METHODS AND COMPOSITIONS FOR ENHANCING DELIVERY OF DOUBLE-STRANDED RNA OR A DOUBLE-STRANDED HYBRID NUCLEIC ACID TO REGULATE GENE EXPRESSION IN MAMMALIAN CELLS
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United States of America Patent
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Issued Date -
Jul 21, 2016
app pub date -
Dec 15, 2015
filing date -
Dec 15, 2015
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Abandoned
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Abstract
Cholesterol moieties are linked to specific ends of double-stranded RNA, preferably a small, interfering (si)RNA or to a dsHybrid. The dsHybrid has one strand comprised of DNA and one strand comprised of RNA. Preferably the sense strand is the DNA strand and the antisense strand is the RNA strand of the dsHybrid. The present invention is based upon the discovery that a cholesterol moiety, if linked to a specific end or ends of the sense or antisense strands of a siRNA, can enhance the delivery and silencing efficiency of the siRNA directed against its target message, in comparison with a corresponding, non-conjugated siRNA. Conjugated siRNAs and dsHybrids of the invention are optionally formulated with, or coordinately administered with, a secondary delivery-enhancing agent, such as a delivery-enhancing peptide, to enhance intracellular delivery and uptake of the conjugated siRNAs or dsHybrid.
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