University of Massachusetts

Worcester Foundation for Experimental Biology

Canadian Patents & Development Ltd.

Cold Spring Harbor Laboratory

John Goodchild

Paul C Zamecnik

Saran A Narang

Ahmad I Bukhari, Deceased

The present invention provides methods for increasing ribozyme catalytic activity without reducing specificity, which methods comprise contacting an RNA molecule with a ribozyme having a flanking sequence modified to contain 2&prime;-O-substituted nucleotides. The invention also provides ribozymes comprising a flanking sequence modified to contain 2&prime;-O-substituted nucleotides. In addition, the invention provides methods for increasing ribozyme catalytic activity comprising contacting an RNA molecule with a ribozyme having a flanking sequence modified to contain a 2&prime;-O-substituted nucleotide and a facilitator oligonucleotide. The present invention further provides compositions comprising a ribozyme having modified flanking sequences and an effective amount of a facilitator oligonucleotide.

Ribozymes having 2&prime;-O substituted nucleotides in the flanking sequences

Methods are disclosed for increasing ribozyme catalytic activity without reducing specificity, which methods comprise contacting an RNA molecule with a ribozyme and a 2'-O-substituted facilitator oligonucleotide. The present invention further provides compositions comprising a ribozyme and an effective amount of a 2'-O-methyl substituted facilitator oligonucleotide. The use of a facilitator, particularly a 2'-O-substituted facilitator, and more especially a 2'-O-methyl substituted facilitator, greatly enhances ribozyme catalytic activity, frequently making an otherwise inactive ribozyme active.

Enhancement of ribozyme catalytic activity by A 2'-O-substituted

Methods are disclosed for increasing ribozyme catalytic activity without reducing specificity, which methods comprise contacting an RNA molecule with a ribozyme and a facilitator oligonucleotide. The present invention further provides compositions comprising a ribozyme and an effective amount of a facilitator oligonucleotide.

Enhancement of ribozyme catalytic activity by a neighboring facilitator

Transposable linkers are DNA sequences recognized and employed by transposition proteins, including transposases, in the insertion of genetic information into the genetic architecture of an organism and in the movement of genetic information from one location to another in the genetic architecture of an organism. Such linkers, comprising the extreme ends of transposons, often referred to as left and right attachment sites, have been isolated from the intervening material in transposons to produce a basic building block comprising simply the extreme ends of the transposons fused together. Using restriction endonuclease recognition sites outside and between the left and right attachment sites it is possible to introduce desired genes directly or via cloning vehicles, into the genetic material of an organism. A transposable linker may also be used to introduce a desired gene, that has been placed in a cloning vehicle but is not, of itself, part of a normally transposable sequence, into the genetic material of an organism.

Transposable linkers to transfer genetic information

Inhibition of HTLV-III by adminstration of an oligonucleotide complementary to highly conserved regions of the HTLV-III genome necessary for HTLV-III replication and/or gene expression is described, as are oligodeoxynucleotide sequences which are complementary to those regions, methods of inhibiting HTLV-III replication and gene expression and methods of determining the presence or absence of HTLV-III virus in samples such as blood, saliva, urine and tears.

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Worcester, MA, United States of America

John Goodchild