High throughput RNAi based functional genomics in primary cells and in vivo

DESCRIPTION provided by applicant Completion of the HGP human genome program has opened the andapos Genomic Eraandapos in biomedical research and enables functional genomics analysis of various gene elements The long term goal of the ENCODE Project is to identify and functionally characterize all of the sequence based genomic elements Functional elements that have been studied in ENCODE include transcribed sequences regulators of transcription and regulators of RNA transcripts themselves The function of more than of transcribed gene sequences is unknown Most of them are expressed in specialized cells and thus their functions can only be studied in a biologically relevant context i e primary cells in vivo In this propoal we plan to develop and commercialize a new RNAi platform that enables gene studies in a biologically relevant context with a long term goal of building a functional map of human genome Introduction of small interfering RNAs siRNAs into cells with transfection reagents results in efficient gene silencing siRNA based functional genomics is widely used in established cell lines in vitro but its applicability to primary cells and in vivo target validatin has been limited because of lack of efficient and non toxic delivery systems In collaboration with RXi pharmaceuticals we have developed a novel class of RNAi compounds self deliverable RNAs These small asymmetric hydrophobically modified RNA compounds enter cells and tissues without requirement for delivery formulation and efficiently silence genes in vitro and in vivo enabling functional genomics studies in primary cells embryonic cells tissues ex vivo and in vivo The major technical hurdle which impedes wide spread use of this platform by scientific community is the complex and costly process of compound identification synthesis and validation The focus of this fast track proposal is optimization of compound discovery process Phase I and development of a panel of functionally validated sdRNAs Phase II Completion of this proposal will build a commercially available product platform that will revolutionize functional genomics studies in biologically relevant systems such as primary cells stem cells tissue and organ models and eventually in vivo This proposal is focused on development and commercialization of a new RNAi platform that enables gene studies in a biologically relevant context with a long term goal of building a functional map of human genome sdRNAs are small asymmetric hydrophobically modified compounds that enter cell and tissues without requirement for delivery formulation and efficiently silence genes in vitro and in vivo The focus of this proposal is developing and making available to scientific community a panel of of sdRNA compounds to enable HTS functional genomics analysis in primary cells stem cells tissues and in vivo