Infectious Particle Composition and Methods of Use Thereof
Description of Invention:
Current methods for delivery of small interfering RNA (siRNA) and short hairpin RNA (shRNA) such as cationic lipid or polyplex delivery systems, do not efficiently deliver siRNAs or shRNAs into a wide range of cell types. Subsequent innovations have resulted in shRNA, but not siRNA, expression cassettes that have been adapted to be compatible with most DNA-based viral vector systems including retroviruses, adenoviruses, lentiviruses, and adeno-associated viruses. As with the transfer of cDNAs, all of these delivery systems require a significant degree of optimization and are often only useful in specific cell systems. Additionally, some viral vectors also have the disadvantage of low titer and large genome size. Further, some of the above viral delivery systems are dependent on helper viruses or packaging cell lines, and some are not able to transduce non-dividing cells, or cells in suspension. Also inherent in current DNA viral delivery systems is a lack of efficiency in delivering the DNA or RNA of interest to the nucleus. Instead, the DNA vector and concomitant siRNA insert remains in the cytoplasm.
siRNA is emerging as a powerful tool for gene silencing and has much potential for anticancer and antiviral applications. However, efficient delivery of these specific siRNAs to the nucleus of a cell is an important aspect of interfering with specific DNA transcription. The present invention provides compositions and methods for use of infectious particles, such as papovavirus pseudovirions, to deliver siRNAs into a variety of mammalian cells. More specifically, the infectious particles may comprise the SV40 capsid protein VP1, papilloma virus capsid protein L1, polyoma virus capsid protein VP1, or several SV40 capsid proteins. The claims further comprise methods for in vivo transfer of siRNA as well as a kit comprising the infectious particle and instructions for use as a siRNA delivery system. This pseudovirions technology has proved to be an excellent alternative to DNA-viral vectors for siRNA delivery with high capacity, very high efficiency, and no viral DNA complications. The pseudovirion delivery technology is described in the following background publications: Kimchi-Sarfaty et al., Human Gene Therapy 13: 299-310, 2002; Kimchi-Sarfaty et al., Human Gene Therapy 14: 167-177, 2003; and Kimchi-Sarfaty et al., Gene Ther Mol Biol 8: 439-450, 2004.
Inventors:
Chava Kimchi-Sarfaty and Michael M. Gottesman (NCI)
Patent Status:
DHHS Reference No. E-138-2005/0-US-01 Licensing Status:
This technology is available for licensing on an exclusive or a non-exclusive basis. In addition to licensing, the technology is available for further development through collaborative research opportunities with the inventors.
Portfolios: Gene Based Therapies
Gene Based Therapies -Therapeutics-Oligonucleotide Based Therapies-Delivery Mechanisms Gene Based Therapies -Therapeutics-Gene Therapy-Delivery Systems Gene Based Therapies -Therapeutics
For Additional Information Please Contact: Michelle A. Booden Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
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Phone: (301)451-7337
Email: boodenm@mail.nih.gov
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