METHODS AND COMPOSITIONS FOR ENHANCING DELIVERY OF DOUBLE-STRANDED RNA OR A DOUBLE-STRANDED HYBRID NUCLEIC ACID TO REGULATE GENE EXPRESSION IN MAMMALIAN CELLS
Mohammad Ahmadian,Kunyuan Cui,Lishan Chen,Shu-Chih Chen Quay,Michael E. Houston, JR.
申请号：
US14970529
公开号：
US20160206749A1
申请日:
2015.12.15
申请国别(地区):
US
年份:
2016
代理人:
摘要：
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.
