TRANSGENIC ANIMAL MODEL FOR SPLICEOSOME-MEDIATED RNA TRANS-SPLICING
Abstract:
The present invention relates to development of an animal model system for in vivo testing of spliceosome-mediated RNA trans -splicing reactions. The present invention provides transgenic animals, and methods for generating such animals, that have been genetically engineered to expresses a target precursor messenger RNA molecule (target pre-mRNA) that serves as a substrate for a trans -splicing reaction. Specifically, the transgenic animals contain at least one transgene capable of expressing a target pre-mRNA molecule. The invention provides methods, based on utilization of the transgenic animals, for assessing the specificity and efficiency of a pre- trans -splicing molecule (PTM) designed to interact with a target pre-mRNA and mediate a trans -splicing reaction resulting in the generation of a novel chimeric RNA molecule. The present invention further relates to the transgenic expression of PTM molecules in animals to determine gene function, i.e , functional genetics. The present invention is based on the successful generation of a transgenic animal expressing a target pre-mRNA and, moreover, the use of that animal to detect accurate in vivo trans -splicing reactions in the presence of a PTM.
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