Out-licensing

The biological phenomenon of RNA interference (RNAi) has much promise for developing therapeutics to a variety of diseases.  However, development of RNAi therapies remains mainly in preclinical stages largely because of difficulties in delivering small inhibitory RNAs (siRNA) and short hairpin RNAs (shRNA) into target cells.  Although viral vector-based siRNA delivery systems have been widely used, their specificity and safety remains significant issue.  Without a solution to this delivery problem, RNAi cannot fulfill its therapeutic promise.

Investigators at the National Institutes of Health have developed novel compositions and methods for delivering inhibitory oligonucleotides to cells in a targeted and efficient manner.  The compositions and methods are based on utilizing a cell surface receptor targeting ligand, such as cytokine or chemokine, and a domain that binds an inhibitory oligonucleotide, to efficiently deliver the inhibitory oligonucleotide to the cell that expresses the cell surface receptor targeting ligand.  Chemokine receptors are differentially expressed on various cells, including tumors; hence this technology allows targeting siRNA to aberrant cells.  Gene silencing can also be achieved in variety of immune cells by targeting cytokine receptors.  This technology has great potential for developing into a safe and effective means of delivering therapeutic siRNAs.

Applications:

• Treatment of cancers and autoimmune diseases by delivery of siRNA to tumor cells or various aberrantly functioning immune cells.
• This technology can be used to boost vaccine responses against cancers and chronic infectious diseases.
• Targeted delivery of fluorochrome-labeled RNA both in vitro and in vivo for diagnostic purposes, for example, to trace or localize various cells and to determine tumor metastasis and aberrant proliferation or homing of immune cells.

Advantages:

• Simple method for linking siRNA to polypeptides to create non-covalent or covalent complexes
• In vivo targeted delivery of inhibitory RNAs into cells rather than systemically
• Delivery of multiple inhibitory RNAs to target multiple genes
• Long term repression of target gene expression through RNAi phenomenon

Development Status: 

Currently animal model studies planned

U.S. Provisional Application No. 61/045,088 filed 15 Apr 2008 (HHS Reference No. E-051-2008/0-US-01)

Inventors: 

Arya Biragyn, Purevdorj Olkhanud and Juan Espinoza (NIA)

Licensees Sought: 

Available for exclusive or non-exclusive licensing.

Collaborative Research Opportunity:  

The National Institute on Aging, Immunotherapeutics Unit, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize chemokine-based siRNA/shRNA technology for treatment of cancers and autoimmune diseases, i.e. to control expression of immunomodulatory cytokines and other factors that facilitate tumor escape, activity of regulatory T cells or Th2 type of cells.  This technology can be also utilized to boost vaccine responses against cancers and chronic infectious diseases.  Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.