Methods and compositions for inhibition of RNA splicing
AssigneesGeron Corporation, University of Rochester
InventorsStephen M. Testa, Matthew D. Disney, Sergei M. Gryaznov, Douglas H. Turner
Life of this patent
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Abstract
A method of inhibiting the self-splicing of a Group I intron is disclosed. The method uses an oligonucleotide having a sequence essentially identical to a guide sequence found in the 5′ flanking exon and terminates with a 3′ ribonucleoside. Usually the oligonucleotide has N3′→P5′ phosphoramidate or N3′→P5′ thiophiosphoramidate linkages rather than phosphodiester linkages. A method of inhibiting the growth of organisms having Group I intron, particularly certain pathogenic fungi including P. carinii, C. albicans, and A. nidulans using the oglionucleotide is also provided.
Claims19
An inhibitor of a Group I intron self-splicing reaction comprising an oligonucleotide having a polynucleotide sequence that binds to a 5′ internal guide sequence of a precursor RNA containing a Group I intron, or to a portion thereof, wherein said oligonucleotide binds to the 5′ internal guide sequence of the precursor RNA and trans-splices to the 3′ exon of the precursor RNA, and wherein said oligonucleotide comprises at least one polynucleotide sequence chosen from SEQ ID No:1, SEQ ID No:2, SEQ ID No:3, and SEQ ID No:9.
A method of inhibiting self-splicing of a Group I intron comprising contacting a precursor RNA containing a Group I intron with an oligonucleotide, wherein said oligonucleotide trans-splices to a 3′ exon sequence of said precursor RNA and inhibits self-splicing of the Group I intron.
A method for inhibiting the growth of an organism transcribing a precursor RNA containing a Group I intron comprising contacting said organism with an amount of an oligonucleotide effective for growth inhibition, wherein said oligonucleotide trans-splices to a 3′ exon sequence of said precursor RNA and inhibits self-splicing of the Group I intron, wherein inhibition of self-splicing of the Group I intron inhibits the growth of the organism.
A method of designing an inhibitor of Group I intron splicing comprising choosing a nucleotide sequence that binds to a 5′ internal guide sequence present in precursor RNA containing a Group I intron, or to a portion thereof, and preparing an oligonucleotide having the chosen sequence, wherein said oligonucleotide binds to the 5′ internal guide sequence of the precursor RNA and trans-splices to the 3′ exon of the precursor RNA.
Dependencies are inferred from the claim text.