期刊
NUCLEIC ACIDS RESEARCH
卷 46, 期 5, 页码 2185-2196出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gky037
关键词
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资金
- CHDI Foundation [A6367]
- Bill and Melissa Gates foundation [OPP1086170]
- [RO1GM1088030181]
- [RO1NS038194]
- [5F32NS095508-03]
- [UH3TR000888]
- [S10 OD 020012-01]
- Bill and Melinda Gates Foundation [OPP1086170] Funding Source: Bill and Melinda Gates Foundation
Small interfering RNA (siRNA)-based drugs require chemical modifications or formulation to promote stability, minimize innate immunity, and enable delivery to target tissues. Partially modified siRNAs (up to 70% of the nucleotides) provide significant stabilization in vitro and are commercially available; thus are commonly used to evaluate efficacy of bioconjugates for in vivo delivery. In contrast, most clinically-advanced non-formulated compounds, using conjugation as a delivery strategy, are fully chemically modified (100% of nucleotides). Here, we compare partially and fully chemically modified siRNAs in conjugate mediated delivery. We show that fully modified siRNAs are retained at 100x greater levels in various tissues, independently of the nature of the conjugate or siRNA sequence, and support productive mRNA silencing. Thus, fully chemically stabilized siRNAs may provide a better platform to identify novel moieties (peptides, aptamers, small molecules) for targeted RNAi delivery.
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