Cleavage of targeted RNA by RNAase P

Details Cleavage of targeted RNA by RNAase P Cleavage of targeted RNA by RNAase P

1990-08-17

1992-12-01

Schwartz, Richard A.

Chemistry: molecular biology and microbiology

Micro-organism, tissue cell culture or enzyme using process...

Preparing compound containing saccharide radical

4351721, 435194, 514 44, 536 27, 935 16, C12P 1934, C12N 910, C12N 1500, A61K 3170

Patent

active

051680530

ABSTRACT:
It has been discovered that it is possible to target any RNA molecule for cleavage by RNase P by forming a hybrid region consisting of a short sequence of base pairs followed by a terminal 3'- NCCA sequence. In the preferred embodiment, the region is formed by addition of an external guide sequence consisting of a nucleotide sequence complementary to the targeted site which includes a 3'-NCCA, wherein the sequence hybridizes to the targeted RNA to form a short sequence of double-stranded RNA under conditions promoting cleavage of the substrate at the nucleotide at the 5' side of the base-paired region by the RNase P or catalytically active equivalent thereof. Specificity is determined by the complementary sequence. The sequence is preferably ten to fifteen nucleotides in length and may contain non-complementary nucleotides to the extent this does not interfere with formation of several base pairs followed by a NCCA at the 3' end. These embodiments are particularly useful in the treatment of viral diseases and disorders associated with expression of specific proteins from mRNA.

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