Cell specific delivery of modified mRNA expressing therapeutic proteins to leukocytes
Open accessAbstract
Therapeutic alteration of gene expression in vivo can be achieved by delivering nucleic acids (e.g., mRNA, siRNA) using nanoparticles. Recent progress in modified messenger RNA (mmRNA) synthesis facilitated the development of lipid nanoparticles (LNPs) loaded with mmRNA as a promising tool for in vivo protein expression. Although progress have been made with mmRNA-LNPs based protein expression in hepatocytes, cell specificity is still a major challenge. Moreover, selective protein expression is essential for an improved therapeutic effect, due to the heterogeneous nature of diseases. Here, we present a precision protein expression strategy in Ly6c + inflammatory leukocytes in inflammatory bowel disease (IBD) induced mice. We demonstrate a therapeutic effect in an IBD model by targeted expression of the interleukin 10 in Ly6c + inflammatory leukocytes. A selective mmRNA expression strategy has tremendous therapeutic potential in IBD and can ultimately become a novel therapeutic modality in many other diseases.
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Targeted LNPs can be administered systemically to target both localized and disseminated cells.
“Moreover, targeted LNPs can be administered systemically to target both localized and disseminated (such as metastatic and/or hematopoietic) cells (22, 23).”
From CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy (2020) · cites this paper as [22]
The targeting strategy designed using the ASSET linker system is the first example of targeted CRISPR-Cas9 therapeutic gene editing for treating metastatic tumors.
“The targeting strategy we designed, using the ASSET linker system (22, 23), is, to our knowledge, the first example of targeted CRISPR-Cas9 therapeutic gene editing for treating metastatic tumors.”
From CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy (2020) · cites this paper as [22]
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- Authors
- Veiga, N., Goldsmith, M., Granot, Y., Rosenblum, D., Dammes, N., Kedmi, R., Ramishetti, S., & Peer, D.
- Affiliations
- Tel Aviv University (IL)
- Corresponding author
- Peer, Dan
- Venue
- Nature Communications
- Published
- 2018-10-29
- Volume
- 9
- Issue
- 1
- Pages
- 4493-4493
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6206083
- OpenAlex
- W2897535855
- Cited by
- 308
- References
- 23
- Citations by year
- 2026: 26 · 2025: 43 · 2024: 55 · 2023: 47 · 2022: 53 · 2021: 43 · 2020: 28 · 2019: 13
- FWCI
- 7.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- EC | European Research Council (647410)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- modified mRNA, lipid nanoparticles, IL-10, inflammatory bowel disease, in vivo protein expression, nanotherapeutics
- MeSH terms
- RAW 264.7 Cells, Animals, Antigens, Ly, Colitis, Disease Models, Animal, Female, Leukocytes, Lipids, Mice, Inbred C57BL, RNA, Messenger, Drug Delivery Systems, Interleukin-10, Mice, Nanoparticles
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