Mechanisms and optimization of in vivo delivery of lipophilic siRNAs

By C. Wolfrum, S. Shi, K. Jayaprakash, M. Jayaraman, Gang Wang, R. Pandey, K. G. Rajeev, T. Nakayama, Klaus Charrise, Esther Ndungo and 4 more. Nature Biotechnology, 2007

956 citations recorded by the source corpus.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5ec3f6d4d816cb6a3330ace4c6d9e89fe5d68b11

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Citations in the corpus

First-in-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement. (2013, background): “Various nanoparticle formulations have been evaluated for their ability to silence targets in vivo (6-10); among these, lipid nanoparticles (LNPs) have been shown to be highly effective in delivering siRNAs to the liver and silencing a number of different hepatocyte gene targets across multiple spec”
In vivo genome editing using Staphylococcus aureus Cas9 (2015, methodology): “One week after intravenous administration of virus into C57BL/6 mice, we observed ~5% indel formation in liver tissue; after four weeks, the liver tissue showed characteristic hepatic lipid accumulation from Apob knockdown following histology analysis using oil red staining 34–37 (Extended Data Fig.”
siRNA delivery systems for cancer treatment. (2009, background): “The fatty acid conjugates with longer, saturated, alkyl chains, such as stearoyl and docosanyl, but not those with shorter chains, reduced target gene expression in mouse livers [88].”
Chemistry, structure and function of approved oligonucleotide therapeutics (2023, background): “between siRNA and plasma lipoproteins, uptake and tissue distribution (370).”
The delivery of therapeutic oligonucleotides (2016, result): “Similar effects were seen with other lipidic conjugates including -tocopherol and long chain fatty acids (247,248).”
Current prospects for RNA interference-based therapies (2011, background): “Lipophilic siRNAs can also bind high-density lipoprotein (HDL); this can target siRNAs to tissues with HDL receptors, such as gut 47 , kidney 47 and vaginal 48 epithelial cells and oligodendrocytes in the brain 49 .”
Designer vaccine nanodiscs for personalized cancer immunotherapy (2016, neutral): “Compared with other HDLs containing 243-amino acid ApoA1 purified from human plasma or produced recombinantly 20-22 , sHDL nanodiscs are synthesized with 22-mer peptides (22A), derived from the repeat α -helix domain of ApoA1 23 , with no sequence homology to endogenous ApoA1, thus averting…”
RNA interference in the clinic: challenges and future directions (2010, background): “HDL-bound siRNAs are predominately taken up by the liver, adrenals, ovaries and kidneys by high-affinity binding to scavenger receptor class B, type I, and LDL-bound siRNAs predominately enter the liver by LDL receptor expressio”