The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Multiparametric approach for the evaluation of lipid nanoparticles for siRNA delivery
Open accessAbstract
Nanoparticle-mediated siRNA delivery is a complex process that requires transport across numerous extracellular and intracellular barriers. As such, the development of nanoparticles for efficient delivery would benefit from an understanding of how parameters associated with these barriers relate to the physicochemical properties of nanoparticles. Here, we use a multiparametric approach for the evaluation of lipid nanoparticles (LNPs) to identify relationships between structure, biological function, and biological activity. Our results indicate that evaluation of multiple parameters associated with barriers to delivery such as siRNA entrapment, pK a , LNP stability, and cell uptake as a collective may serve as a useful prescreening tool for the advancement of LNPs in vivo. This multiparametric approach complements the use of in vitro efficacy results alone for prescreening and improves in vitro–in vivo translation by minimizing false negatives. For the LNPs used in this work, the evaluation of multiple parameters enabled the identification of LNP pK a as one of the key determinants of LNP function and activity both in vitro and in vivo. It is anticipated that this type of analysis can aid in the identification of meaningful structure–function–activity relationships, improve the in vitro screening process of nanoparticles before in vivo use, and facilitate the future design of potent nanocarriers.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“Endosomal escape can be increased by optimizing the pKa values of ionizable lipids66,76–78,88,100,140.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [140]
In the citing paper
“Moreover, the delivery efficacy of mRNA could be improved, for example, by rational design of lipids through modulation of head groups and hydrophobic tails to increase cellular uptake and endosomal escape of lipid nanoparticle–mRNA formulations64,66,76–78,88,97,100,114,140,141.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [140]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Knocking down barriers: advances in siRNA delivery
Whitehead, K. A., Langer, R., & Anderson, D. G. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2742 · Cited by 3,115
Self-citationThe effect of particle design on cellular internalization pathways
Gratton, S. E. A., Ropp, P. A., Pohlhaus, P. D., Luft, J. C., Madden, V. J., Napier, M. E., & DeSimone, J. M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801763105 · Cited by 2,918
Rational design of cationic lipids for siRNA delivery
Semple, S. C., Akinc, A., Chen, J., Sandhu, A. P., Mui, B. L., Cho, C. K., Sah, D. W. Y., Stebbing, D., Crosley, E. J., Yaworski, E., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1602 · Cited by 1,822
Endosomal escape pathways for delivery of biologicals
Varkouhi, A. K., Scholte, M., Storm, G., & Haisma, H. J. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.11.004 · Cited by 1,561
Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo
Jayaraman, M., Ansell, S. M., Mui, B. L., Tam, Y. K., Chen, J., Du, X., Butler, D., Eltepu, L., Matsuda, S., Narayanannair, J. K., et al. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201203263 · Cited by 1,267
Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms
Akinc, A., Querbes, W., De, S., Qin, J., Frank-Kamenetsky, M., Jayaprakash, K. N., Jayaraman, M., Rajeev, K. G., Cantley, W. L., Dorkin, J. R., et al. (2010) · Molecular Therapy · doi:10.1038/mt.2010.85 · Cited by 1,261
A combinatorial library of lipid-like materials for delivery of RNAi therapeutics
Akinc, A., Zumbuehl, A., Goldberg, M., Leshchiner, E. S., Busini, V., Hossain, N., Bacallado, S. A., Nguyen, D. N., Fuller, J., Alvarez, R., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1402 · Cited by 1,150
Self-citationDavis, M. E. (2009) · Molecular Pharmaceutics · doi:10.1021/mp900015y · Cited by 979
Lipid-like materials for low-dose, in vivo gene silencing
Love, K. T., Mahon, K. P., Levins, C. G., Whitehead, K. A., Querbes, W., Dorkin, J. R., Qin, J., Cantley, W., Qin, L. L., Racie, T., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910603106 · Cited by 969
Self-citationTherapeutic siRNA silencing in inflammatory monocytes in mice
Leuschner, F., Dutta, P., Gorbatov, R., Novobrantseva, T. I., Donahoe, J. S., Courties, G., Lee, K. M., Kim, J. I., Markmann, J. F., Marinelli, B., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1989 · Cited by 839
Self-citationDelivery of siRNA Therapeutics: Barriers and Carriers
Wang, J., Lu, Z., Wientjes, M. G., & Au, J. L. ‐. (2010) · The AAPS Journal · doi:10.1208/s12248-010-9210-4 · Cited by 820
Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes
Rozema, D. B., Lewis, D. L., Wakefield, D. H., Wong, S. C., Klein, J. J., Roesch, P. L., Bertin, S. L., Reppen, T. W., Chu, Q., Blokhin, A. V., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703778104 · Cited by 667
Breaking down the barriers: siRNA delivery and endosome escape
Domińska, M., & Dykxhoorn, D. M. (2010) · Journal of Cell Science · doi:10.1242/jcs.066399 · Cited by 640
Bartlett, D. W. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkj439 · Cited by 601
Cationic lipid saturation influences intracellular delivery of encapsulated nucleic acids
Heyes, J., Palmer, L., Bremner, K., & MacLachlan, I. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.06.014 · Cited by 572
A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium
Santel, A., Aleku, M., Keil, O., Endruschat, J., Esche, V., Fisch, G., Dames, S., Löffler, K., Fechtner, M., Arnold, W., et al. (2006) · Gene Therapy · doi:10.1038/sj.gt.3302777 · Cited by 368
Nucleic Acid Delivery: The Missing Pieces of the Puzzle?
Nguyen, J., & Szoka, F. C. (2012) · Accounts of Chemical Research · doi:10.1021/ar3000162 · Cited by 356
Development of Lipidoid–siRNA Formulations for Systemic Delivery to the Liver
Akinc, A., Goldberg, M., Qin, J., Dorkin, J. R., Gamba-Vitalo, C., Maier, M., Jayaprakash, K. N., Jayaraman, M., Rajeev, K. G., Manoharan, M., et al. (2009) · Molecular Therapy · doi:10.1038/mt.2009.36 · Cited by 323
Self-citationpH Homeostasis of Cellular Organelles
Demaurex, N. (2002) · Physiology · doi:10.1152/physiologyonline.2002.17.1.1 · Cited by 234
Extracellular Glycosaminoglycans Modify Cellular Trafficking of Lipoplexes and Polyplexes
Ruponen, M., Rönkkö, S., Honkakoski, P., Pelkonen, J., Tammi, M., & Urtti, A. O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011553200 · Cited by 208
Merkel, O. M., Librizzi, D., Pfestroff, A., Schurrat, T., Buyens, K., Sanders, N. N., Smedt, S. C. D., Béhé, M. P., & Kissel, T. (2009) · Journal of Controlled Release · doi:10.1016/j.jconrel.2009.05.016 · Cited by 181
Modulation of Membrane Fusion by Asymmetric Transbilayer Distributions of Amino Lipids
Bailey, A. L., & Cullis, P. R. (1994) · Biochemistry · doi:10.1021/bi00208a007 · Cited by 143
Systemic RNAi-mediated Gene Silencing in Nonhuman Primate and Rodent Myeloid Cells
Novobrantseva, T. I., Borodovsky, A., Wong, J., Klebanov, B., Zafari, M. R., Yucius, K., Querbes, W., Ge, P., Ruda, V. M., Milstein, S., et al. (2012) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2011.3 · Cited by 137
Self-citationBuyens, K., Lucas, B., Raemdonck, K., Braeckmans, K., Vercammen, J., Hendrix, J., Engelborghs, Y., Smedt, S. C. D., & Sanders, N. N. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.10.024 · Cited by 133
In Vitro–In Vivo Translation of Lipid Nanoparticles for Hepatocellular siRNA Delivery
Whitehead, K. A., Matthews, J., Chang, P., Niroui, F., Dorkin, J. R., Severgnini, M., & Anderson, D. G. (2012) · ACS Nano · doi:10.1021/nn301922x · Cited by 130
Self-citationHobo, W. A., Novobrantseva, T. I., Fredrix, H., Wong, J., Milstein, S., Epstein-Barash, H., Liu, J., Schaap, N. P., van der Voort, R., & Dolstra, H. (2012) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-012-1334-1 · Cited by 127
Kwon, Y. J. (2011) · Accounts of Chemical Research · doi:10.1021/ar200241v · Cited by 127
Quantitative Analysis of Synthetic Gene Delivery Vector Design Properties
Varga, C. M., Hong, K., & Lauffenburger, D. A. (2001) · Molecular Therapy · doi:10.1006/mthe.2001.0475 · Cited by 120
Cell‐surface glycosaminoglycans inhibit cation‐mediated gene transfer
Ruponen, M., Honkakoski, P., Tammi, M., & Urtti, A. O. (2004) · The Journal of Gene Medicine · doi:10.1002/jgm.522 · Cited by 112
Tang, Y., Li, Y.-B., Wang, B., Lin, R.-Y., van Dongen, M. A., Zurcher, D. M., Gu, X.-Y., Holl, M. M. B., Liu, G., & Qi, R. (2012) · Molecular Pharmaceutics · doi:10.1021/mp3001364 · Cited by 99
Zhang, J., Fan, H., Levorse, D. A., & Crocker, L. S. (2011) · Langmuir · doi:10.1021/la104590k · Cited by 96
Philipp, A. B., Zhao, X. B., Tarcha, P. J., Wagner, E., & Zintchenko, A. (2009) · Bioconjugate Chemistry · doi:10.1021/bc9001536 · Cited by 87
Phospholipid, cholesterol, polypeptide and glycoprotein composition of hepatic endosome subfractions
Evans, W. H., & Hardison, W. G. M. (1985) · Biochemical Journal · doi:10.1042/bj2320033 · Cited by 83
FRET-Labeled siRNA Probes for Tracking Assembly and Disassembly of siRNA Nanocomplexes
Alabi, C. A., Love, K. T., Sahay, G., Stutzman, T., Young, W. T., Langer, R., & Anderson, D. G. (2012) · ACS Nano · doi:10.1021/nn3013838 · Cited by 67
Self-citationAttacking the genome: emerging siRNA nanocarriers from concept to clinic
Alabi, C. A., Vegas, A. J., & Anderson, D. G. (2012) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2012.05.004 · Cited by 53
Self-citationZhang, J., Fan, H., Levorse, D. A., & Crocker, L. S. (2011) · Langmuir · doi:10.1021/la201464k · Cited by 48
Sulakhe, P. V., & Dhalla, N. S. (1970) · PubMed · Cited by 46
Mescalchin, A., Detzer, A., Wecke, M., Overhoff, M. G., Wünsche, W., & Sczakiel, G. (2007) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.7.10.1531 · Cited by 40
Nanocarriers: a tool to overcome biological barriers in siRNA delivery
Kumari, A., Kumar, V., & Yadav, S. K. (2011) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2011.587801 · Cited by 9
Research works printed but not linked: 1
- K Fitzgerald, et al. Phase I safety, pharmacokinetic and pharmacodynamic results for ALN-PCS: A novel RNAi therapeutic for the treatment of hypercholesterolemia (Alnylam Pharmaceuticals, Cambridge, MA, Available at http://www.alnylam.com/capella/wp-content/uploads/2012/04/ALN-PCS-PhaseI-ATVB-April20-2012.pdf. Accessed September 8, 2012. (2012).
Cited by
Sorted by citations
Lipid nanoparticles for mRNA delivery
Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00358-0 · Cited by 4,076
Self-citationNon-viral vectors for gene-based therapy
Yin, H., Kanasty, R. L., Eltoukhy, A. A., Vegas, A. J., Dorkin, J. R., & Anderson, D. G. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3763 · Cited by 3,123
Self-citationmRNA vaccines for infectious diseases: principles, delivery and clinical translation
Chaudhary, N., Weissman, D., & Whitehead, K. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00283-5 · Cited by 1,555
Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown
Wittrup, A., Ai, A., Liu, X., Hamar, P., Trifonova, R., Charisse, K., Manoharan, M., Kirchhausen, T., & Lieberman, J. (2015) · Nature Biotechnology · doi:10.1038/nbt.3298 · Cited by 693
Liu, S., Cheng, Q., Wei, T., Yu, X., Johnson, L. T., Farbiak, L., & Siegwart, D. J. (2021) · Nature Materials · doi:10.1038/s41563-020-00886-0 · Cited by 653
Metadata
- Authors
- Alabi, C. A., Love, K. T., Sahay, G., Yin, H., Luly, K. M., Langer, R., & Anderson, D. G.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- University of Rochester (US)
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142;
- Harvard–MIT Division of Health Sciences and Technology (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-07-23
- Volume
- 110
- Issue
- 32
- Pages
- 12881-12886
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3740846
- OpenAlex
- W2155534998
- Cited by
- 188
- References
- 39
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 26 · 2023: 9 · 2022: 13 · 2021: 18 · 2020: 11 · 2019: 11 · 2018: 9 · 2017: 8 · 2016: 17 · 2015: 16 · 2014: 15 · 2013: 3
- FWCI
- 7.62
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Institutes of Health (4r37eb000244-34)
- National Cancer Institute (P30CA014051)
- National Institute of Biomedical Imaging and Bioengineering (R37-EB000244)
- 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 › Advancements in Transdermal Drug Delivery
- Keywords
- lipid nanoparticles, siRNA delivery, cellular uptake, in vitro to in vivo translation, nanocarrier design
- MeSH terms
- Animals, Factor VII, Flow Cytometry, HeLa Cells, Hemolysis, Humans, Lipids, Luciferases, Mice, Inbred C57BL, Reproducibility of Results, Gene Transfer Techniques, Microscopy, Confocal, Fluorescence Resonance Energy Transfer, RNA Interference, RNA, Small Interfering, Mice, Nanoparticles
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.
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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
