To: foxtrot who wrote (291 ) 12/8/1999 5:06:00 AM From: Thomas Read Replies (1) | Respond to of 562
Another RZYM patent courtesy of CompanySleuth.com. I like the sounds of it. Anything they can do to improve half life inccreases our chances of seeing ribozymes demonstrate efficacy. Cheers, Thomas United States Patent 5,998,203 Matulic-Adamic , et al. December 7, 1999 -------------------------------------------------------------------------------- Enzymatic nucleic acids containing 5'-and/or 3'-cap structures SUMMARY OF THE INVENTION This invention relates to the incorporation of chemical modifications at the 5' and/or 3' ends of nucleic acids, which are particularly useful for enzymatic cleavage of RNA or single-stranded DNA. These terminal modifications are termed as either a 5'-cap or a 3'-cap depending on the terminus that is modified. Certain of these modifications protect the enzymatic nucleic acids from exonuclease degradation. Resistance to exonuclease degradation can increase the half-life of these nucleic acids inside a cell and improve the overall effectiveness of the enzymatic nucleic acids. These terminal modifications can also be used to facilitate efficient uptake of enzymatic nucleic acids by cells, transport and localization of enzymatic nucleic acids within a cell, and help achieve an overall improvement in the efficacy of ribozymes in vitro and in vivo. The term "chemical modification" as used herein refers to any base, sugar and/or phosphate modification that will protect the enzymatic nucleic acids from degradation by nucleases. Non-limiting examples of some of the chemical modifications and methods for their synthesis and incorporation in nucleic acids are described in FIGS. 7, 8, 11-16 and infra. In a preferred embodiment, chemical modifications of enzymatic nucleic acids are featured that provide resistance to cellular 5'-exonuclease and/or 3'-exonuclease digestion without reducing the catalytic activity or cellular efficacy of these nucleic acids.