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Cited by 144Extracellular vesicles in diseaseRNA Interference and Gene DeliveryNanoparticle-Based Drug Delivery

Exosome for mRNA delivery: Strategies and therapeutic applications

Open access
Iqbal, Zoya, Rehman, Khurrum, Mahmood, Ayesha, Shabbir, Maryam, Liang, Yujie, Duan, Li, Zeng, Hui·2024·Journal of Nanobiotechnology
DOI 10.1186/s12951-024-02634-xPMC PMC11225225
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Abstract

Messenger RNA (mRNA) has emerged as a promising therapeutic molecule with numerous clinical applications in treating central nervous system disorders, tumors, COVID-19, and other diseases. mRNA therapies must be encapsulated into safe, stable, and effective delivery vehicles to preserve the cargo from degradation and prevent immunogenicity. Exosomes have gained growing attention in mRNA delivery because of their good biocompatibility, low immunogenicity, small size, unique capacity to traverse physiological barriers, and cell-specific tropism. Moreover, these exosomes can be engineered to utilize the natural carriers to target specific cells or tissues. This targeted approach will enhance the efficacy and reduce the side effects of mRNAs. However, difficulties such as a lack of consistent and reliable methods for exosome purification and the efficient encapsulation of large mRNAs into exosomes must be addressed. This article outlines current breakthroughs in cell-derived vesicle-mediated mRNA delivery and its biomedical applications. Graphical Abstract

AI snapshot

Written from the paper’s full text.

TL;DR

Exosomes are reviewed as biocompatible, low-immunogenicity mRNA delivery vehicles that can be engineered for targeted delivery across biological barriers. The review surveys loading strategies, surface/genetic modification approaches, and therapeutic applications while emphasizing unresolved purification, loading, dosing, and clinical-translation challenges.

Key findings

  • Exosomes offer advantages for mRNA delivery including biocompatibility, low immunogenicity, small size, ability to cross physiological barriers, cell-specific tropism, and evasion of the mononuclear phagocytic system; they can be engineered chemically or genetically for targeting.
  • Loading strategies include endogenous/pre-loading methods (passive and active) and exogenous/post-loading methods (electroporation, cellular nanoporation, transfection reagents, exosome-liposome hybrids). Reported quantitative examples include >100-fold increase in Ldlr mRNA in donor cells/exosomes, TAMEL-mediated up to sixfold RNA cargo loading and 40-fold enrichment with VSVG, CNP increasing mRNA encapsulation efficiency 3–4 folds and mRNA loading 100-fold versus conventional electroporation, and electroporation loading about one-fifth of Cas9 mRNA into erythrocyte-derived EVs.
  • Therapeutic applications span cancer, CNS disease, infectious disease, metabolic disorders, and cardiovascular disease. Examples include catalase mRNA-loaded exosomes reducing 6-OHDA-induced neuroinflammation in a Parkinson’s disease model, Bmp7 mRNA delivery inducing white adipose browning, and exosome-based SARS-CoV-2 N/S mRNA vaccine inducing humoral and cellular immunity.
  • Major barriers remain: inconsistent exosome purification, inefficient encapsulation of large mRNAs, low drug loading/retention, rapid clearance, difficult production/isolation/purification, and limited clinical trials.

Methods

  • Narrative review of exosome-mediated mRNA delivery, covering mRNA therapy advances/challenges, exosome biogenesis and uptake, cargo-loading strategies, exosome modification for targeting, and biomedical applications.
  • Synthesizes preclinical and clinical literature and includes Table 1 comparing mRNA delivery carriers and Table 2 listing potential exosome-mRNA applications by disease, source cell line, targeted moiety, and outcome.
  • No primary experimental data, systematic search strategy, or meta-analysis is described.

Limitations

  • Stated in the paper: lack of consistent and reliable exosome purification methods; technical difficulty encapsulating large mRNAs; limited clinical trials; low drug loading and retention; rapid clearance from blood; difficult production, isolation, and purification; undetermined optimal mRNA dosage; need for improved targeting/tissue specificity; potential immunogenicity; and scale-up/manufacturing challenges.
  • Evident from the text: this is a narrative review without a described systematic search or quantitative synthesis, and many cited therapeutic findings are preclinical or animal-model studies, so clinical applicability remains uncertain.
  • Evident from the text: mechanisms such as how exosomes cross biological barriers and general rules controlling cargo loading/transport are described as not fully understood.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1186/s12951-024-02634-x

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 118 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    mRNA therapies must be encapsulated into safe, stable, and effective delivery vehicles to preserve the cargo from degradation and prevent immunogenicity.

    “mRNA therapies must be encapsulated into safe, stable, and effective delivery vehicles to preserve the cargo from degradation and prevent immunogenicity.”
    • Also stated in: § Introduction · plain
      “To ensure cargo protection and effective delivery into the cytoplasm of target cells, they must be enclosed in nanocarriers.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [7] Gao M, Zhang Q, Feng XH, Liu J. Synthetic modified messenger RNA for therapeutic applications. Acta Biomater. 2021;131:1–15. source

      Not checked in the free run.

    • cites [8] Ho W, Gao M, Li F, Li Z, Zhang XQ, Xu X. Next-generation vaccines: nanoparticle-mediated DNA and mRNA delivery. Adv Healthc Mater. 2021;10: e2001812. source

      Not checked in the free run.

  • Premisecitation

    mRNA has emerged as a promising therapeutic molecule with numerous clinical applications in treating central nervous system disorders, tumors, COVID-19, and other diseases.

    “Messenger RNA (mRNA) has emerged as a promising therapeutic molecule with numerous clinical applications in treating central nervous system disorders, tumors, COVID-19, and other diseases.”
    • Also stated in: § Introduction · boosted
      “Nucleic acid-based treatments, particularly messenger RNA (mRNA), have played a pivotal role in recent advances in RNA-based vaccination, protein replacement therapy, gene editing, and cancer immunotherapy [2]. Recently, two mRNA vaccines targeting severe acute respiratory coronavirus type 2 (SARS-CoV-2) were licensed to prevent COVID-19 infection [3–6].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [2] Kaczmarek JC, Kowalski PS, Anderson DG. Advances in the delivery of RNA therapeutics: from concept to clinical reality. Genome Med. 2017;9:60. source

      Not checked in the free run.

    • cites [3] Fang E, Liu X, Li M, Zhang Z, Song L, Zhu B, Wu X, Liu J, Zhao D, Li Y. Advances in COVID-19 mRNA vaccine development. Signal Transduct Target Ther. 2022;7:94. source

      Not checked in the free run.

    • cites [4] Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384:403–16. source

      Not checked in the free run.

    • cites [5] Szabó GT, Mahiny AJ, Vlatkovic I. COVID-19 mRNA vaccines: platforms and current developments. Mol Ther. 2022;30:1850–68. source

      Not checked in the free run.

    • cites [6] Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, Perez JL, Pérez Marc G, Moreira ED, Zerbini C, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383:2603–15. source

      Not checked in the free run.

  • Premisecitation

    Exosomes can express surface proteins and receptors of their donor cells, allowing them to target recipient cells within the same tissue effectively.

    “One of the key benefits of exosomes is their ability to express surface proteins and receptors of their donor cells, allowing them to target recipient cells within the same tissue effectively. For example, lung spheroid cell-derived exosomes can deliver vaccines directly to lung tissue [82].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [82] Popowski KD, Moatti A, Scull G, Silkstone D, Lutz H, de Juan L, Abad B, George A, Belcher E, Zhu D, Mei X, et al. Inhalable dry powder mRNA vaccines based on extracellular vesicles. Matter. 2022;5:2960–74. source

      Not checked in the free run.

  • Premisecitation

    Exosomes provide a protective microenvironment for the loaded cargoes.

    “Exosomes provide a protective microenvironment for the loaded cargoes. The lipid bilayers of exosomes protect mRNA from degradation by extracellular enzymes, ensuring its integrity and stability during transit to target cells [75].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [75] Chaudhari P, Ghate V, Nampoothiri M, Lewis S. Multifunctional role of exosomes in viral diseases: from transmission to diagnosis and therapy. Cell Signal. 2022;94: 110325. source

      Not checked in the free run.

  • Premisecitation

    Many obstacles still exist despite the rise in studies on delivery platforms, including toxicity and the precise distribution of mRNA to extrahepatic organs.

    “Many obstacles still exist despite the rise in studies on delivery platforms, including toxicity and the precise distribution of mRNA to extrahepatic organs [13, 14].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [13] Dowdy SF. Overcoming cellular barriers for RNA therapeutics. Nat Biotechnol. 2017;35:222–9. source

      Not checked in the free run.

    • cites [14] Cheng Q, Wei T, Farbiak L, Johnson LT, Dilliard SA, Siegwart DJ. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR-Cas gene editing. Nat Nanotechnol. 2020;15:313–20. source

      Not checked in the free run.

  • May combine two claims. 40
  • Classified as probably not a substantial claim. 2
  • The quote only partly states this claim. 6

  • May combine two claims.

    Premisecitation

    Exosomes have gained growing attention in mRNA delivery because of their good biocompatibility, low immunogenicity, small size, unique capacity to traverse physiological barriers, and cell-specific tropism.

    “Exosomes have gained growing attention in mRNA delivery because of their good biocompatibility, low immunogenicity, small size, unique capacity to traverse physiological barriers, and cell-specific tropism.”
    • Also stated in: § Introduction · plain
      “Exosomes have gained particular interest in the field of mRNA delivery due to their unique ability to cross physiological barriers, favorable biocompatibility, low toxicity, cell-specific tropism, and ability to evade the mononuclear phagocytic system [16, 17].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [16] Wu P, Zhang B, Ocansey DKW, Xu W, Qian H. Extracellular vesicles: a bright star of nanomedicine. Biomaterials. 2021;269: 120467. source

      Not checked in the free run.

    • cites [17] Sil S, Dagur RS, Liao K, Peeples ES, Hu G, Periyasamy P, Buch S. Strategies for the use of extracellular vesicles for the delivery of therapeutics. J Neuroimmune Pharmacol. 2020;15:422–42. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Preclinical studies have demonstrated the benefits of exosome-based mRNA therapies, which are moving toward clinical trials.

    “Preclinical studies have demonstrated the benefits of exosome-based mRNA therapies, which are moving toward clinical trials [88].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [88] Li T, Li X, Han G, Liang M, Yang Z, Zhang C, Huang S, Tai S, Yu S. The therapeutic potential and clinical significance of exosomes as carriers of drug delivery system. Pharmaceutics. 2022;15:21. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Engineered exosomes can deliver mRNA to specific sites, avoid immune system detection and early degradation, overcome biological barriers, and even control the release of the drug in response to a specific external stimulus.

    “Engineered exosomes can deliver mRNA to specific sites, avoid immune system detection and early degradation, overcome biological barriers, and even control the release of the drug in response to a specific external stimulus [18, 19].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [18] Zhang X, Zhang H, Gu J, Zhang J, Shi H, Qian H, Wang D, Xu W, Pan J, Santos HA. Engineered extracellular vesicles for cancer therapy. Adv Mater. 2021;33: e2005709. source

      Not checked in the free run.

    • cites [19] Man K, Brunet MY, Jones MC, Cox SC. Engineered extracellular vesicles: tailored-made nanomaterials for medical applications. Nanomaterials. 1838;2020:10.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The main obstacle to the delivery of mRNA lies in its intrinsic instability and inability to penetrate the cellular lipid bilayer.

    “The main obstacle to the delivery of mRNA lies in its intrinsic instability and inability to penetrate the cellular lipid bilayer.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [7] Gao M, Zhang Q, Feng XH, Liu J. Synthetic modified messenger RNA for therapeutic applications. Acta Biomater. 2021;131:1–15. source

      Not checked in the free run.

    • cites [8] Ho W, Gao M, Li F, Li Z, Zhang XQ, Xu X. Next-generation vaccines: nanoparticle-mediated DNA and mRNA delivery. Adv Healthc Mater. 2021;10: e2001812. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Difficulties such as a lack of consistent and reliable methods for exosome purification and the efficient encapsulation of large mRNAs into exosomes must be addressed.

    “However, difficulties such as a lack of consistent and reliable methods for exosome purification and the efficient encapsulation of large mRNAs into exosomes must be addressed.”
    • Also stated in: § Strategies for mRNA loading into exosomes · plain
      “However, using exosome-based mRNA delivery systems has several limitations, such as the technical difficulties in generating exosomes loaded with RNA [91]. Encapsulating large RNAs, e.g., mRNA, into exosomes is also a technical challenge [92].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [91] Stewart MP, Sharei A, Ding X, Sahay G, Langer R, Jensen KF. In vitro and ex vivo strategies for intracellular delivery. Nature. 2016;538:183–92. source

      Not checked in the free run.

    • cites [92] Usman WM, Pham TC, Kwok YY, Vu LT, Ma V, Peng B, Chan YS, Wei L, Chin SM, Azad A, et al. Efficient RNA drug delivery using red blood cell extracellular vesicles. Nat Commun. 2018;9:2359. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exosomes can be genetically engineered, chemically surface modified or enzymatically engineered to introduce peptides and proteins to enhance their targeting ability.

    “In addition, exosomes can be genetically engineered, chemically surface modified or enzymatically engineered to introduce peptides and proteins to enhance their targeting ability [42, 83–86].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [42] Liang Y, Iqbal Z, Wang J, Xu L, Xu X, Ouyang K, Zhang H, Lu J, Duan L, Xia J. Cell-derived extracellular vesicles for CRISPR/Cas9 delivery: engineering strategies for cargo packaging and loading. Biomater Sci. 2022;10:4095–106. source

      Not checked in the free run.

    • cites [83] Xu M, Feng T, Liu B, Qiu F, Xu Y, Zhao Y, Zheng Y. Engineered exosomes: desirable target-tracking characteristics for cerebrovascular and neurodegenerative disease therapies. Theranostics. 2021;11:8926–44. source

      Not checked in the free run.

    • cites [84] Liang Y, Xu X, Li X, Xiong J, Li B, Duan L, Wang D, Xia J. Chondrocyte-targeted microRNA delivery by engineered exosomes toward a cell-free osteoarthritis therapy. ACS Appl Mater Interfaces. 2020;12:36938–47. source

      Not checked in the free run.

    • cites [85] Liu Q, Li D, Pan X, Liang Y. Targeted therapy using engineered extracellular vesicles: principles and strategies for membrane modification. J Nanobiotechnol. 2023;21:334. source

      Not checked in the free run.

    • cites [86] Xu X, Liang Y, Li X, Ouyang K, Wang M, Cao T, Li W, Liu J, Xiong J, Li B, et al. Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration. Biomaterials. 2021;269: 120539. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Compared to synthetic delivery systems, exosomes administered in vivo result in fewer immunogenic reactions, toxicity, and adverse effects due to their biocompatible nature.

    “Compared to synthetic delivery systems, exosomes administered in vivo result in fewer immunogenic reactions, toxicity, and adverse effects due to their biocompatible nature. This makes exosomes a safer and more efficient option for mRNA delivery [81].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [81] Wang J, Zhu M, Nie G. Biomembrane-based nanostructures for cancer targeting and therapy: from synthetic liposomes to natural biomembranes and membrane-vesicles. Adv Drug Deliv Rev. 2021;178: 113974. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Unmodified mRNAs can trigger inflammation and immune reactions when introduced into the body as foreign invaders, thus compromising efficacy and safety.

    “Unmodified mRNAs can trigger inflammation and immune reactions when introduced into the body as foreign invaders, thus compromising efficacy and safety [52].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [52] Pandey M, Ojha D, Bansal S, Rode AB, Chawla G. From bench side to clinic: potential and challenges of RNA vaccines and therapeutics in infectious diseases. Mol Aspects Med. 2021;81: 101003. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Exosomes can be engineered to target specific cells or tissues, which will enhance the efficacy and reduce the side effects of mRNAs.

    “Moreover, these exosomes can be engineered to utilize the natural carriers to target specific cells or tissues. This targeted approach will enhance the efficacy and reduce the side effects of mRNAs.”
    • Also stated in: § Introduction · plain
      “Engineered exosomes can deliver mRNA to specific sites, avoid immune system detection and early degradation, overcome biological barriers, and even control the release of the drug in response to a specific external stimulus [18, 19].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [18] Zhang X, Zhang H, Gu J, Zhang J, Shi H, Qian H, Wang D, Xu W, Pan J, Santos HA. Engineered extracellular vesicles for cancer therapy. Adv Mater. 2021;33: e2005709. source

      Not checked in the free run.

    • cites [19] Man K, Brunet MY, Jones MC, Cox SC. Engineered extracellular vesicles: tailored-made nanomaterials for medical applications. Nanomaterials. 1838;2020:10.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The biofilm coverage of exosomes allows them to avoid degradation by macrophages, hence prolonging their circulation time.

    “Furthermore, the biofilm coverage of exosomes allows them to avoid degradation by macrophages, hence prolonging their circulation time [76].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [76] Shen M, Shen Y, Fan X, Men R, Ye T, Yang L. Roles of macrophages and exosomes in liver diseases. Front Med. 2020;7: 583691. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exosomes have gained particular interest in the field of mRNA delivery due to their unique ability to cross physiological barriers, favorable biocompatibility, low toxicity, cell-specific tropism, and ability to evade the mononuclear phagocytic system.

    “Exosomes have gained particular interest in the field of mRNA delivery due to their unique ability to cross physiological barriers, favorable biocompatibility, low toxicity, cell-specific tropism, and ability to evade the mononuclear phagocytic system [16, 17].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [16] Wu P, Zhang B, Ocansey DKW, Xu W, Qian H. Extracellular vesicles: a bright star of nanomedicine. Biomaterials. 2021;269: 120467. source

      Not checked in the free run.

    • cites [17] Sil S, Dagur RS, Liao K, Peeples ES, Hu G, Periyasamy P, Buch S. Strategies for the use of extracellular vesicles for the delivery of therapeutics. J Neuroimmune Pharmacol. 2020;15:422–42. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Active pre-loading methods require transfection of donor cells with specific plasmids, which may be more labor-intensive and time-consuming compared to passive pre-loading methods.

    “Although active pre-loading methods have advantages in selectively targeting candidate mRNAs and increasing RNA cargo loading, they require the transfection of donor cells with specific plasmids, which may be more labor-intensive and time-consuming compared to passive pre-loading methods.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Engineered exosomes carrying RVG-Lamp2b can efficiently cross the blood-brain barrier and deliver catalase mRNA, resulting in a reduction of 6-OHDA-mediated neuroinflammation in a mouse model of Parkinson's disease.

    “The designed exosome carrying RVG-Lamp2b was able to efficiently cross the blood–brain barrier (BBB) and deliver the catalase mRNA, resulting in a reduction of 6-OHDA-mediated neuroinflammation in a mouse model of Parkinson’s disease [101, 103].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [101] Kojima R, Bojar D, Rizzi G, Hamri GC, El-Baba MD, Saxena P, Ausländer S, Tan KR, Fussenegger M. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment. Nat Commun. 2018;9:1305. source

      Not checked in the free run.

    • cites [103] Liang Y, Iqbal Z, Lu J, Wang J, Zhang H, Chen X, Duan L, Xia J. Cell-derived nanovesicle-mediated drug delivery to the brain: Principles and strategies for vesicle engineering. Mol Ther. 2023;31:1207–24. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CNP technology increases exosome yield and mRNA amount within exosomes.

    “The CNP technology increases the exosome yield and the mRNA amount within the exosomes [110].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [110] Yang Z, Shi J, Xie J, Wang Y, Sun J, Liu T, Zhao Y, Zhao X, Wang X, Ma Y, et al. Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation. Nat Biomed Eng. 2020;4:69–83. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    miR-155 encapsulated in these exosomes can be efficiently delivered to recipient cells and target endogenous molecules.

    “Moreover, miR-155 encapsulated in these exosomes can be efficiently delivered to recipient cells and target endogenous molecules (Fig. 2C) [105].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [105] Li Z, Zhou X, Wei M, Gao X, Zhao L, Shi R, Sun W, Duan Y, Yang G, Yuan L. In Vitro and in Vivo RNA inhibition by CD9-HuR functionalized exosomes encapsulated with miRNA or CRISPR/dCas9. Nano Lett. 2019;19:19–28. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    These findings demonstrate the prospective application of engineered exosome delivery platforms in converting primary T cells into CAR T cells directly, furnishing a new approach for in vivo CAR T cell production.

    “These findings demonstrate the prospective application of engineered exosome delivery platforms in converting primary T cells into CAR T cells directly, furnishing a new approach for in vivo CAR T cell production [106].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [106] Si K, Dai Z, Li Z, Ye Z, Ding B, Feng S, Sun B, Shen Y, Xiao Z. Engineered exosome-mediated messenger RNA and single-chain variable fragment delivery for human chimeric antigen receptor T-cell engineering. Cytotherapy. 2023;25:615–24. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Electroporation can load approximately one-fifth of Cas9 mRNA into EVs derived from erythrocytes.

    “Previous studies have demonstrated that electroporation can load approximately one-fifth of Cas9 mRNA into EVs derived from erythrocytes [92].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [92] Usman WM, Pham TC, Kwok YY, Vu LT, Ma V, Peng B, Chan YS, Wei L, Chin SM, Azad A, et al. Efficient RNA drug delivery using red blood cell extracellular vesicles. Nat Commun. 2018;9:2359. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Liposomal structures can easily load mRNA and DNA, but are not efficient in delivering these therapeutic substances to target cells.

    “Although liposomal structures can easily load mRNA and DNA, they are not efficient in delivering these therapeutic substances to target cells [112].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [112] Kiaie SH, Mojarad-Jabali S, Khaleseh F, Allahyari S, Taheri E, Zakeri-Milani P, Valizadeh H. Axial pharmaceutical properties of liposome in cancer therapy: recent advances and perspectives. Int J Pharm. 2020;581: 119269. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    These exosomes promoted collagen grafts formation and reduced formation of wrinkles in photoaging dermal collagen depletion mice model.

    “These exosomes promoted the collagen grafts formation and reduced the formation of wrinkles in the photoaging dermal collagen depletion mice model.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [111] You Y, Tian Y, Yang Z, Shi J, Kwak KJ, Tong Y, Estania AP, Cao J, Hsu WH, Liu Y, et al. Intradermally delivered mRNA-encapsulating extracellular vesicles for collagen-replacement therapy. Nat Biomed Eng. 2023;7:887–900. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    When PTEN mRNA was modified with CDX peptide, resulting exosomes exhibited a twofold increase in accumulation in mouse U87 gliomas, leading to prolonged survival.

    “Moreover, when PTEN mRNA was additionally modified with the CDX peptide, the resulting exosomes exhibited a twofold increase in accumulation in mouse U87 gliomas, leading to prolonged survival.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [110] Yang Z, Shi J, Xie J, Wang Y, Sun J, Liu T, Zhao Y, Zhao X, Wang X, Ma Y, et al. Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation. Nat Biomed Eng. 2020;4:69–83. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Overall therapeutic effect was improved while minimizing unintended effects on non-target tissues.

    “As a result, the overall therapeutic effect was improved while minimizing unintended effects on non-target tissues (Fig. 6) [121].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [121] Sun W, Xing C, Zhao L, Zhao P, Yang G, Yuan L. Ultrasound assisted exosomal delivery of tissue responsive mRNA for enhanced efficacy and minimized off-target effects. Mol Ther Nucleic Acids. 2020;20:558–67. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exosomes utilized to transport PGC1α mRNA, responsive to miR-148a and specific to adipose tissue, achieved successful delivery to targeted adipose tissue through ultrasound-guided microvesicle disruption.

    “Exosomes were utilized to transport PGC1α mRNA, which is responsive to miR-148a and specific to adipose tissue. Through microvesicle disruption guided by ultrasound, the system achieved successful delivery to the targeted adipose tissue.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [121] Sun W, Xing C, Zhao L, Zhao P, Yang G, Yuan L. Ultrasound assisted exosomal delivery of tissue responsive mRNA for enhanced efficacy and minimized off-target effects. Mol Ther Nucleic Acids. 2020;20:558–67. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Modification of PTEN mRNA with CREKA peptide resulted in a 1.5-fold increase in accumulation in mouse U87 gliomas and improved survival.

    “Similarly, modification of PTEN mRNA with CREKA peptide resulted in a 1.5-fold increase in accumulation in mouse U87 gliomas and improved survival [110].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [110] Yang Z, Shi J, Xie J, Wang Y, Sun J, Liu T, Zhao Y, Zhao X, Wang X, Ma Y, et al. Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation. Nat Biomed Eng. 2020;4:69–83. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Injection of MV containing CD-UPRT mRNA/protein directly into schwannomas resulted in significantly high expression of functional proteins and inhibition of tumor growth following systemic treatment with prodrug 5-FC.

    “The injection of this system directly into schwannomas resulted in significantly high expression of functional proteins and inhibition of tumor growth following systemic treatment with the prodrug 5-FC.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [125] Mizrak A, Bolukbasi MF, Ozdener GB, Brenner GJ, Madlener S, Erkan EP, Ströbel T, Breakefield XO, Saydam O. Genetically engineered microvesicles carrying suicide mRNA/protein inhibit schwannoma tumor growth. Mol Ther. 2013;21:101–8. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    EXOtic system carrying RVG-Lamp2b successfully crossed the BBB and delivered catalase mRNA.

    “The developed system carrying RVG-Lamp2b successfully crossed the BBB and delivered catalase mRNA.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [101] Kojima R, Bojar D, Rizzi G, Hamri GC, El-Baba MD, Saxena P, Ausländer S, Tan KR, Fussenegger M. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment. Nat Commun. 2018;9:1305. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    This engineered exosome delivery system has great potential for converting primary T cells into CAR T cells and provides a new approach for in vivo induction of CAR T cells.

    “The results suggested that this engineered exosome delivery system has great potential for converting primary T cells into CAR T cells and provides a new approach for the in vivo induction of CAR T cells [106].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [106] Si K, Dai Z, Li Z, Ye Z, Ding B, Feng S, Sun B, Shen Y, Xiao Z. Engineered exosome-mediated messenger RNA and single-chain variable fragment delivery for human chimeric antigen receptor T-cell engineering. Cytotherapy. 2023;25:615–24. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Interpretationcitation

    This study demonstrates the effectiveness of MV in delivering therapeutic proteins and mRNAs to treat various diseases.

    “This study demonstrates the effectiveness of MV in delivering therapeutic proteins and mRNAs to treat various diseases [125].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [125] Mizrak A, Bolukbasi MF, Ozdener GB, Brenner GJ, Madlener S, Erkan EP, Ströbel T, Breakefield XO, Saydam O. Genetically engineered microvesicles carrying suicide mRNA/protein inhibit schwannoma tumor growth. Mol Ther. 2013;21:101–8. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This method effectively enhanced expression of PGC1α protein, particularly in mouse adipose tissue, while reducing expression in other tissues such as lung.

    “This method effectively enhanced the expression of PGC1α protein, particularly in mouse adipose tissue, while reducing expression in other tissues such as the lung.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [121] Sun W, Xing C, Zhao L, Zhao P, Yang G, Yuan L. Ultrasound assisted exosomal delivery of tissue responsive mRNA for enhanced efficacy and minimized off-target effects. Mol Ther Nucleic Acids. 2020;20:558–67. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Bursts release of NGF protein was observed, and the system exhibited a high degree of stability on storage, allowing it to function effectively in vivo for extended periods.

    “Bursts release of NGF protein was observed, and the system exhibited a high degree of stability on storage, allowing it to function effectively in vivo for extended periods (Fig. 5) [124].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [124] Yang J, Wu S, Hou L, Zhu D, Yin S, Yang G, Wang Y. Therapeutic effects of simultaneous delivery of nerve growth factor mRNA and protein via exosomes on cerebral ischemia. Mol Ther Nucleic Acids. 2020;21:512–22. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Findings suggest that inflammation can be reduced by modulating microglia polarization, highlighting this system's potential for treating stroke.

    “The findings suggest that inflammation can be reduced by modulating microglia polarization, highlighting this system's potential for treating stroke.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Application of KK-(EK)4-lipids to exosomes and lipid nanoparticles encapsulating mRNA increased cellular association and enhanced protein expression in vitro for modified exosomes and mRNA-LNPs, respectively, compared to unmodified nanocarrier.

    “Application of KK-(EK)4-lipids to exosomes and lipid nanoparticles encapsulating mRNA increased cellular association and enhanced protein expression in vitro for modified exosomes and mRNA-LNPs, respectively, compared to the unmodified nanocarrier.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [126] Sugimoto Y, Suga T, Umino M, Yamayoshi A, Mukai H, Kawakami S. Investigation of enhanced intracellular delivery of nanomaterials modified with novel cell-penetrating zwitterionic peptide-lipid derivatives. Drug Deliv. 2023;30:2191891. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CP05-TK-mPEG switchable stealth core-decorating exosomes loaded with Ce6 and Bmp7 mRNA can locally degrade by ultrasound, resulting in precise delivery of Bmp7 mRNA to omental adipose tissue of obese mice.

    “CP05-TK-mPEG switchable stealth core-decorating exosomes were developed and loaded with Chlorin e6 (Ce6) and bone Bmp7 mRNA. This smart system can locally degrade by ultrasound (US), resulting in precise delivery of Bmp7 mRNA to the omental adipose tissue (OAT) of obese mice (Fig. 4) [97].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [97] Guo Y, Wan Z, Zhao P, Wei M, Liu Y, Bu T, Sun W, Li Z, Yuan L. Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes. J Nanobiotechnology. 2021;19:402. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This reduced neuroinflammation induced by 6-OHDA and neurotoxicity in a Parkinson's mouse model.

    “This reduced neuroinflammation induced by 6-OHDA and neurotoxicity in a Parkinson's mouse model [101].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [101] Kojima R, Bojar D, Rizzi G, Hamri GC, El-Baba MD, Saxena P, Ausländer S, Tan KR, Fussenegger M. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment. Nat Commun. 2018;9:1305. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    Exosomes derived from dendritic cells and HEK-293 loaded with mRNA encoding HChrR6 exhibited selective killing and almost complete suppression of breast cancer in a mouse model.

    “When the designed exosomes were delivered to HER2 + human breast cancer cells, they exhibited selective killing and almost complete suppression of breast cancer in a mouse model.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [122] Li Y, Ma X, Yue Y, Zhang K, Cheng K, Feng Q, Ma N, Liang J, Zhang T, Zhang L, et al. Rapid surface display of mRNA antigens by bacteria-derived outer membrane vesicles for a personalized tumor vaccine. Adv Mater. 2022;34: e2109984. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Yang et al. modified CD47-derived exosomes by incorporating a glioma targeting peptide at N terminus, allowing selective uptake of PTEN cargo by glioma cells and effectively inhibiting tumor cell proliferation.

    “Yang et al. modified CD47-derived exosomes by incorporating a glioma targeting peptide at the N terminus. This modification allowed for selective uptake of tumor suppression gene, phosphatase and tensin homolog (PTEN) cargo by glioma cells. As a result, the proliferation of tumor cells was effectively inhibited [110].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [110] Yang Z, Shi J, Xie J, Wang Y, Sun J, Liu T, Zhao Y, Zhao X, Wang X, Ma Y, et al. Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation. Nat Biomed Eng. 2020;4:69–83. source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    Zhao et al. engineered exosomes using ADSC to treat obesity; smart exosomes reduced WAT inflammation, improved energy expenditure and resilience to obesity progression.

    “The smart exosomes reduced WAT inflammation, improved energy expenditure and resilience to obesity progression [136].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [136] Zhao H, Shang Q, Pan Z, Bai Y, Li Z, Zhang H, Zhang Q, Guo C, Zhang L, Wang Q. Exosomes from adipose-derived stem cells attenuate adipose inflammation and obesity through polarizing M2 macrophages and Beiging in white adipose tissue. Diabetes. 2018;67:235–47. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    Catalase mRNA-loaded exosomes from HEK-293 targeted to brain reduced 6-OHDA-induced neuroinflammation in Parkinson's disease.

    “The study results revealed a reduction of 6-OHDA-induced neuroinflammation in Parkinson’s disease [133].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [133] Chen HX, Liang FC, Gu P, Xu BL, Xu HJ, Wang WT, Hou JY, Xie DX, Chai XQ, An SJ. Exosomes derived from mesenchymal stem cells repair a Parkinson’s disease model by inducing autophagy. Cell Death Dis. 2020;11:288. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exosomes functionalized with RVG and loaded with NGF-mRNA reduced inflammation and promoted cell survival on systemic administration, exhibiting promising therapeutic potential for stroke.

    “On systemic administration, the system reduced inflammation and promoted cell survival, thus exhibiting the promising therapeutic potential for stroke.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [124] Yang J, Wu S, Hou L, Zhu D, Yin S, Yang G, Wang Y. Therapeutic effects of simultaneous delivery of nerve growth factor mRNA and protein via exosomes on cerebral ischemia. Mol Ther Nucleic Acids. 2020;21:512–22. source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    Mizrak et al. engineered genetically modified exosomes from HEK-293 carrying mRNA/protein encoding CD and UPRT to treat schwannomas; CD converted prodrug 5-FC into active form 5-FU, inhibiting DNA synthesis and leading to apoptosis of cancer cells.

    “The study revealed that CD converted the prodrug (5-FC) into its active form (5-FU), and consequentially, the DNA synthesis was inhibited, leading to the apoptosis of cancer cells [122].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [122] Li Y, Ma X, Yue Y, Zhang K, Cheng K, Feng Q, Ma N, Liang J, Zhang T, Zhang L, et al. Rapid surface display of mRNA antigens by bacteria-derived outer membrane vesicles for a personalized tumor vaccine. Adv Mater. 2022;34: e2109984. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Popowski et al. developed an inhalable vaccine utilizing lung-derived exosomes for mRNA and protein cargos; Lung-Exo exhibited pronounced mRNA translation, protein expression, and improved cargo retention in bronchioles and parenchyma, suggesting better therapeutic efficacy against SARS-CoV-2.

    “They indicated that Lung-Exo exhibited pronounced mRNA translation, protein expression, and improved cargo retention in bronchioles and parenchyma, suggesting better therapeutic efficacy against severe acute respiratory syndrome coronavirus -2 (SARS-COV-2) [135].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [135] Popowski KD, de Juan López, Abad B, George A, Silkstone D, Belcher E, Chung J, Ghodsi A, Lutz H, Davenport J, Flanagan M, et al. Inhalable exosomes outperform liposomes as mRNA and protein drug carriers to the lung. Extracell Vesicle. 2022;1:100002. source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    Localized US-assisted delivery of Bmp7 using decorated exosomes elicited efficient browning of OAT and proved promising anti-obesity therapy.

    “The study results revealed that localized US-assisted delivery of Bmp7 elicited efficient browning of OAT and proved as a promising anti-obesity therapy [97].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [97] Guo Y, Wan Z, Zhao P, Wei M, Liu Y, Bu T, Sun W, Li Z, Yuan L. Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes. J Nanobiotechnology. 2021;19:402. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Forterre et al. developed IVT HChrR6 mRNA-exosomes and revealed selective uptake by HER2 cancer cells without toxicity to other cells and very insignificant compromise to bone marrow.

    “Forterre et al. developed in vitro transcribed (IVT) HChrR6 mRNA-exosomes and revealed selective uptake by HER2 cancer cells without toxicity to other cells and very insignificant compromise to bone marrow.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [134] Forterre AV, Wang JH, Delcayre A, Kim K, Green C, Pegram MD, Jeffrey SS, Matin AC. Extracellular vesicle-mediated in vitro transcribed mRNA delivery for treatment of HER2(+) Breast cancer xenografts in mice by prodrug CB1954 without general toxicity. Mol Cancer Ther. 2020;19:858–67. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exosomes loaded with mRNA drugs may be passively transported throughout the body or targeted through surface engineering.

    “Exosomes loaded with mRNA drugs may be passively transported throughout the body or targeted through surface engineering [87].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [87] Kim H, Jang H, Cho H, Choi J, Hwang KY, Choi Y, Kim SH, Yang Y. Recent advances in exosome-based drug delivery for cancer therapy. Cancers. 2021;13:4435. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Exosomes possess several characteristics that make them ideal carriers for drug delivery, e.g., biocompatibility, low immunogenicity, ability to cross the BBB and targeted delivery capabilities.

    “Exosomes possess several characteristics that make them ideal carriers for drug delivery, e.g., biocompatibility, low immunogenicity, ability to cross the BBB and targeted delivery capabilities.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Non-specific uptake of exosomes by non-target tissues is a major obstacle to clinical application of exosome-mediated nucleic acid delivery.
44 of 44

  • The paper relies on this without support.

    Naked mRNA molecules can trigger immune responses due to rapid degradation in the bloodstream.

    “As a result of rapid degradation in the bloodstream, naked mRNA molecules can trigger immune responses.”

  • The paper relies on this without support.

    Exosomes exhibit remarkable stability during blood circulation, permitting them to transport mRNA over long distances in vivo.

    “Notably, exosomes exhibit remarkable stability during blood circulation, permitting them to transport mRNA over long distances in vivo, regardless of normal or pathological conditions.”

  • The paper relies on this without support.

    Traditional cellular cultures cannot produce the required quantities to meet clinical dosage requirements.

    “Traditional cellular cultures cannot produce the required quantities to meet clinical dosage requirements.”

  • The paper relies on this without support.

    Electroporation requires purification and isolation of exosomes before and after transfection, involving high-speed centrifugation that can damage exosomes and compromise sample quality.

    “The process requires purification and isolation of exosomes before and after transfection, which involves high-speed centrifugation that can potentially damage exosomes and compromise sample quality.”

  • The paper relies on this without support.

    The rules that generally control cargo loading and transportation into exosomes are still poorly understood.

    “While some of the motifs that regulate the encapsulation of biomolecules into exosomes have been identified, the rules that generally control cargo loading and transportation are still poorly understood.”

  • The paper relies on this without support.

    Non-specific uptake of exosomes by non-target tissues is a major obstacle to clinical application of exosome-mediated nucleic acid delivery.

    “Nonetheless, a major obstacle to its clinical application is the non-specific uptake of exosome by non-target tissues, leading to off-target effects.”

  • The paper relies on this without support.

    The potential immunogenicity of exosome-mediated mRNA delivery is uncertain and needs investigation.

    “Finally, the potential immunogenicity of exosome-mediated mRNA delivery needs to be thoroughly investigated to ensure their clinical viability.”

  • The paper relies on this without support.

    Current use of nanoparticles for mRNA therapy is limited to laboratory scale.

    “Currently, the use of nanoparticles for mRNA therapy are still limited to the laboratory scale, and further research is needed to advance the use of these techniques at the patient bedside.”
8 of 8

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Exosome-based and exosome-mimicking systems have attracted increasing interest because of intrinsic biocompatibility, tumor-homing potential, and ability to facilitate intracellular transport of functional cargo.

    “In particular, exosome-based and exosome-mimicking systems have attracted increasing interest because of their intrinsic biocompatibility, tumor-homing potential, and ability to facilitate intracellular transport of functional cargo [106,107,108].”

    From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [107]

    The Introduction (page unavailable) says exosomes have attracted interest for their biocompatibility, cell-specific tropism and delivery capacity; the mRNA-delivery section describes cargo uptake and release into the cytosol. The chemical-modification section reports tumor targeting by engineered exosomes. Our copy does not establish that exosome-mimicking systems share all these properties or that tumor homing is intrinsic to exosomes generally. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Schwannoma study is assigned the wrong reference number

    Minor

    The schwannoma passage cites [122], whose bibliography entry is a paper on bacteria-derived outer membrane vesicle tumor vaccines. The bibliography instead lists the Mizrak et al. schwannoma study as [125].

  • Figure 6 cites a different study from the text describing it

    Minor

    The Figure 6 caption attributes the PGC1α illustration to reference [97], but the accompanying text identifies Figure 6 with a study cited as [121]. Reference [97] is titled as a Bmp7 mRNA study.

  • Figure 4 cites a different study from the text describing it

    Minor

    The Figure 4 caption attributes the Bmp7 delivery illustration to reference [121], while the text explicitly identifies Figure 4 with the Bmp7 system cited as [97].

3 of 3

The citation lists haven’t been fetched yet

References 140 · Cited by 144

Authors
Iqbal, Z., Rehman, K., Mahmood, A., Shabbir, M., Liang, Y., Duan, L., & Zeng, H.
Affiliations
  • Shenzhen University (CN)
  • The University Of Agriculture Dera Ismail Khan (PK)
  • University of Lahore (PK)
  • Shenzhen KangNing Hospital (CN)
Corresponding author
  • Liang, Yujie
  • Duan, Li
  • Zeng, Hui
ORCID
Venue
Journal of Nanobiotechnology
Publisher
Springer Science and Business Media LLC
Published
2024-07-04
Volume
22
Issue
1
Pages
395-395
ISSN
1477-3155 (ISSN-L)
DOI
10.1186/s12951-024-02634-x
PMC
PMC11225225
OpenAlex
W4400314015
Semantic Scholar
680e7d8e3bd38c3437239df2a7013e9a08b17bac
Cited by
144
References
140
Citations by year
2026: 71 · 2025: 65 · 2024: 8
FWCI
5.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Nanobiotechnology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Greater South Information System
Funders
  • Ministry of Science and Technology of the People's Republic of China, Project (QN2022032011L)
  • Guangdong Basic and Applied Basic Research Foundation (2023A1515011936)
  • the Shenzhen Fund for Guangdong Provincial High Level Clinical Key Specialties (No. SZGSP013)
  • the Shenzhen Key Medical Discipline Construction Fund (No. SZXK042)
  • the Fund of Development and Reform Commission of Shenzhen Municipality(Shenzhen Engineering Research Center for Precision Psychiatric Technology ). (XMHT20220104028)
  • National Natural Science Foundation of China (No. 81972116)
  • Guangdong International Cooperation Project (No. 2021A0505030011)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
exosomes, mRNA delivery, mRNA therapeutics, exosome engineering, targeted delivery, exosome isolation, immunogenicity, central nervous system disorders, cancer therapy, COVID-19 vaccines, cell-derived vesicles
MeSH terms
COVID-19, SARS-CoV-2, Animals, Humans, Neoplasms, RNA, Messenger, Drug Delivery Systems, Gene Transfer Techniques, Exosomes

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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