Chimeric RNA-driven genomic rearrangement in mammalian cells
AssigneeBaylor College of Medicine
InventorsLaising Yen, Sachin Kumar Gupta, Jocelyn Duen-Ya Jea
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Abstract
Embodiments of the disclosure include methods and compositions in which two inter-chromosomal or intra-chromosomal genomic DNA regions are rearranged upon exposure of the genomic DNA to a chimeric RNA that produces fusion of the two regions. The chimeric RNA hybridizes to the two different parts of the genomic DNA and forms a DNA/RNA hybrid in a sequence-specific manner, thereby facilitating genomic rearrangement. In particular embodiments this mechanism is utilized to produce directed gene fusion in targeted genomic DNA regions.
Claims16
A method of producing a genomic fusion product through endogenous genomic DNA rearrangements between a first and a second region of genomic DNA in a cell, in vitro, comprising the step of:
- exposing to the genomic DNA an effective amount of an exogenously provided synthetic chimeric RNA, said chimeric RNA comprising (1) a first RNA sequence that is reverse complement with respect to a portion of the first region of genomic DNA and (2) a second RNA sequence that is reverse complement with respect to a portion of the second region of genomic DNA, wherein the first RNA sequence is between 30-150 nucleotides long and the second RNA sequence is between 30-150 nucleotides long, wherein a portion of the first genomic region that is not reverse complement to the first RNA sequence is reverse complementary to a portion of the second genomic region that is not reverse complement to the second RNA sequence, and wherein upon exposing of the chimeric RNA to the genomic DNA, the first and second genomic regions become fused to each other thereby producing the genomic fusion product through endogenous DNA recombination.
Dependencies are inferred from the claim text.