Reconstituted High Density Lipoprotein Particles as siRNA Carriers

Project Summary Since the discovery of the Nobel prize winning mechanism of RNA interferenceRNAiten years agoit has become a promising drug target for the treatment of multiple diseasesincluding cancerHoweversignificant barriers still exist on the road to clinical applications of siRNA drugsincluding poor cellular uptakeinstability under physiological conditionsoff target effects and possible immunogenicityThe successful application of siRNA for cancer therapy requires the development of clinically suitablesafe and effective drug delivery systemsWe are developing a novel therapeutic strategy for this cancer by harnessing the power of the body s natural lipoproteins to deliver siRNA specifically to cancer cells that inhibits tumor growthThese siRNA interfere with processes critical to tumorigenesis and metastasisand offer the potential to reverse poor survival outcomesFurtherinhibition of this gene results in increased tumor apoptosiswhich could be leveraged to reduce tumor burdenHerewe present a novel mechanism to deliver the therapeutic siRNA to cancer cells using a reconstituted version of the body s natural high density lipoproteinrHDLThis lipoprotein has a long circulating half life and targets the SR Breceptorwhich is over expressed in most types of ovarian cancer cellsOur in vivo experiments demonstrate siRNA rHDL targets ovarian cancer through the SR BreceptorIt also reduces the tumor burden in orthotopic animal models of cancerThe technology has been granted a patentas well as published in a top tier peer reviewed publicationFannin Partners is a privately held early stage biomedical commercialization company dedicated to the advancement of innovative therapies in early pre clinical developmentThe current innovation is the direct result of ground breaking research conducted by the scientific team of DrAndres Lacko and DrAnil SoodBoth the original inventors will be directly involved in the development of the drugThe focus of this proposal is to accomplish key milestones that will further transition this cancer therapy technology to commercialization by optimizing manufacturing parametersmeasuring distribution to other tissuesmetabolismand eliminationand also give a better understanding of potential toxicities Project Narrative Cancer gene therapy using siRNA is an attractive approach that falls short of expectations due to an absence of appropriate delivery vehiclesWe are developing a novel therapeutic strategy by harnessing the power of the body s natural lipoproteins to deliver small bits of genetic material specifically to cancer cells that inhibit tumor growthIn this studywe propose to optimize the synthetic process of the drug and obtain a more detailed understanding of its toxicology and distribution in animal models