Abstract
RNA interference (RNAi)-based therapeutics are approaching clinical approval for genetically defined diseases. Current clinical success is a result of significant innovations in the development of chemical architectures that support sustained, multi-month efficacy in vivo following a single administration. Conjugate-mediated delivery has established itself as the most promising platform for safe and targeted small interfering RNA (siRNA) delivery. Lipophilic conjugates represent a major class of modifications that improve siRNA pharmacokinetics and enable efficacy in a broad range of tissues. Here, we review current literature and define key features and limitations of this approach for in vivo modulation of gene expression.
Keywords:
delivery; lipid conjugation; siRNA.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Biological Transport
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Gene Transfer Techniques*
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Humans
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Lipids / chemistry*
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Molecular Targeted Therapy / methods
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Neoplasm Proteins / antagonists & inhibitors*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Neoplasms / genetics
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Neoplasms / metabolism
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Neoplasms / pathology
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Neoplasms / therapy*
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Oligonucleotides, Antisense / chemistry
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Oligonucleotides, Antisense / pharmacokinetics*
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Oligonucleotides, Antisense / therapeutic use
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Organ Specificity
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RNA, Small Interfering / chemistry
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RNA, Small Interfering / pharmacokinetics*
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RNA, Small Interfering / therapeutic use
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Xenograft Model Antitumor Assays
Substances
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Lipids
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Neoplasm Proteins
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Oligonucleotides, Antisense
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RNA, Small Interfering