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Transducible Delivery of siRNAs by dsRNA Binding Domain Fusions to PDT/CPPs

详细技术说明: Researchers at UCSD have developed a method to deliver siRNA into cells by reversibly masking or neutralizing the charge on the dsRNA using a fusion protein of the TAT delivery peptide and the dsRNA binding domains (DRBDs). The DRBDs, four DRBDs cover the surface of the dsRNA cylinder, bind specifically to dsRNA and mask approximately 16 bp of dsRNA. Also, the DRBDs bind in a sequence independent manner, so that any siRNA will be able to be delivered by this technique. Aggregation of the conjugate does not occur. Currently, the delivery of siRNA through the cell membrane into the cell is problematic due to the large size and the negative charge. Transfection works, but cannot be done in vivo; viral delivery works but presents other problems; liposomes have also shown limited success. The ability to deliver siRNA in vivo via protein transduction domains will be a significant advance for the potential treatment of many diseases including cancer, viral infections, genetic diseases, etc. The inventors have constructed more than ten variations of multiple TATs with multiple DRBDs and have shown that the TAT-DRBDs bind to and neutralize siRNAs in cell culture. Animal studies have not yet been done.

*Principal Investigation: Name: Steven Dowdy
Department:

Name: Akiko Eguchi
Department:

Name: Bryan Meade
Department:

Name: Jehangir Wadia
Department:

附加资料: Patent Number: US8273867B2
Application Number: US2008278739A
Inventor: Dowdy, Steven F. | Wadia, Jehangir S. | Meade, Bryan | Eguchi, Akiko
Priority Date: 10 Feb 2006
Priority Number: US8273867B2
Application Date: 10 Dec 2008
Publication Date: 25 Sep 2012
IPC Current: C12N001511 | C07H002102
US Class: 5360245 | 530300 | 514044A
Assignee Applicant: The Regents of the University of California
Title: Transducible delivery of siRNA by dsRNA binding domain fusions to PTD/CPPS
Usefulness: Transducible delivery of siRNA by dsRNA binding domain fusions to PTD/CPPS
Summary: The composition and polypeptide are useful for intracellular delivery of nucleic acids or delivering interfering RNA agents, for cellular transduction and cellular modulation, and for treating cell proliferative disorders.
Novelty: New composition comprising nucleic acid binding protein in complex with anionically charged nucleic acid and protein transduction domain, useful for delivering interfering RNA agents or for cellular transduction and cellular modulation

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