The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates
Open accessAbstract
siRNA therapeutics have promise for the treatment of a wide range of genetic disorders. Motivated by lipoproteins, we report lipopeptide nanoparticles as potent and selective siRNA carriers with a wide therapeutic index. Lead material cKK-E12 showed potent silencing effects in mice (ED50 ∼ 0.002 mg/kg), rats (ED50 < 0.01 mg/kg), and nonhuman primates (over 95% silencing at 0.3 mg/kg). Apolipoprotein E plays a significant role in the potency of cKK-E12 both in vitro and in vivo. cKK-E12 was highly selective toward liver parenchymal cell in vivo, with orders of magnitude lower doses needed to silence in hepatocytes compared with endothelial cells and immune cells in different organs. Toxicity studies showed that cKK-E12 was well tolerated in rats at a dose of 1 mg/kg (over 100-fold higher than the ED50). To our knowledge, this is the most efficacious and selective nonviral siRNA delivery system for gene silencing in hepatocytes reported to date.
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?
The cited source says what the claim attributes to it.
In the citing paper
“The delivery of therapeutic RNA molecules (siRNA or microRNA) encapsulated within the lipid or lipid-like carrier231,232 into the cells or tissues was proven to be effective in infectious diseases and tumors, as shown in many preclinical studies233,234,235 and clinical trials (reviewed by Kaczmarek et al.236).”
From MiR-128-3p – a gray eminence of the human central nervous system (2024) · cites this paper as [233]
In the citing paper
“Some other LNPs were reported with organ specificity, such as cKK-E12 lipopeptide nanoparticles, wherein the lipid tails were conjugated to peptide derivatives and achieved liver targeting siRNA delivery.[67]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [67]
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
Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E., & Mello, C. C. (1998) · Nature · doi:10.1038/35888 · Cited by 15,429
Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology
Mahley, R. W. (1988) · Science · doi:10.1126/science.3283935 · Cited by 4,028
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-citationRational 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 · cited 1×
“TTR, primarily synthesized in hepatocytes, plays significant roles in transporting thyroxine and retinol (10).”
BackgroundSelf-citationAbdel‐Magid, A. F., Carson, K. G., Harris, B. D., Maryanoff, C. A., & Shah, R. D. (1996) · The Journal of Organic Chemistry · doi:10.1021/jo960057x · Cited by 1,521
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
Self-citationBio-inspired, bioengineered and biomimetic drug delivery carriers
Yoo, J., Irvine, D. J., Discher, D. E., & Mitragotri, S. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3499 · Cited by 1,251
The promises and pitfalls of RNA-interference-based therapeutics
Castanotto, D., & Rossi, J. J. (2009) · Nature · doi:10.1038/nature07758 · Cited by 1,241
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-citationGenetic Heterogeneity in Human Disease
McClellan, J., & King, M.-C. (2010) · Cell · doi:10.1016/j.cell.2010.03.032 · Cited by 981
Cited by
Sorted by citations
Engineering precision nanoparticles for drug delivery
Mitchell, M. J., Billingsley, M. M., Haley, R. M., Wechsler, M. E., Peppas, N. A., & Langer, R. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0090-8 · Cited by 7,933
Self-citationCancer nanomedicine: progress, challenges and opportunities
Shi, J., Kantoff, P. W., Wooster, R., & Farokhzad, O. C. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2016.108 · Cited by 5,873
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-citationTherapeutic siRNA: state of the art
Hu, B., Zhong, L., Weng, Y., Peng, L., Huang, Y., Zhao, Y., & Liang, X.-J. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0207-x · Cited by 1,586
Drug delivery systems for RNA therapeutics
Paunovska, K., Loughrey, D., & Dahlman, J. E. (2022) · Nature Reviews Genetics · doi:10.1038/s41576-021-00439-4 · Cited by 1,349
Metadata
- Authors
- Dong, Y., Love, K. T., Dorkin, J. R., Sirirungruang, S., Zhang, Y., Chen, D., Bogorad, R. L., Yin, H., Chen, Y., Vegas, A. J., Alabi, C. A., Sahay, G., Olejnik, K. T., Wang, W., Schroeder, A., Lytton-Jean, A. K. R., Siegwart, D. J., Akinc, A., Barnes, C., Barros, S. A., Carioto, M., Fitzgerald, K., Hettinger, J., Kumar, V., Novobrantseva, T. I., Qin, J., Querbes, W., Koteliansky, V., Langer, R., & Anderson, D. G.
- Affiliations
- Boston Children's Hospital (US)
- Massachusetts Institute of Technology (US)
- Koch Institute for Integrative Cancer Research At MIT (US)
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;
- Alnylam Pharmaceuticals (United States) (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-02-10
- Volume
- 111
- Issue
- 11
- Pages
- 3955-3960
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3964096
- OpenAlex
- W2071030419
- Cited by
- 488
- References
- 35
- Citations by year
- 2026: 29 · 2025: 45 · 2024: 53 · 2023: 51 · 2022: 40 · 2021: 42 · 2020: 35 · 2019: 30 · 2018: 29 · 2017: 39 · 2016: 41 · 2015: 36 · 2014: 17
- FWCI
- 18.19
- Type
- journal article
- Language
- en
- Update notices
- correction (2014-03-26)
- Open access
- bronze
- doi.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
- Alnylam Pharmaceuticals
- National Institutes of Health (5r01de016516-10, 4r37eb000244-34, 5-R01-, 1f32eb017625-01, 5r01ca132091-04, CA151884, DE-016516, U54-CA151884, EB-000244, R01-EB000244-27, DE016516-03)
- National Heart, Lung, and Blood Institute (HHSN268201000045C)
- National Cancer Institute (5-R01-CA132091–04, U54CA151884, CA151884, R01-CA132091)
- National Institute of Biomedical Imaging and Bioengineering (R01-EB000244-27, EB-000244, R01EB000244, R37-EB000244, 1F32EB017625, F32 EB017625)
- National Institute of Dental and Craniofacial Research (R01DE016516-03)
- 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
- siRNA delivery, apolipoprotein E, hepatocyte targeting, liver parenchymal cells, siRNA therapeutics, toxicity, rodents, non-human primates, lipoproteins
- MeSH terms
- Animals, Apolipoproteins E, Macaca fascicularis, Drug Delivery Systems, Cryoelectron Microscopy, Gene Silencing, Hepatocytes, RNA, Small Interfering, Mice, Rats, Nanoparticles, Lipopeptides
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
