Adenosine Derivatives in Synthetic Oligonucleotides that Modulate RNA Interference Activity and Off-Target Effects

University of Utah Technology Commercialization Office
posted on 03/31/2011

• request more info 
•   
•  LICENSE ONLINE

Invention Description: Chemically modified RNAs are of great interest in studying the RNA interference pathway. This technology is focused on the chemical modification of nucleoside analogs, such as adenosine, as an approach to study RNA interference and off-target effects. For example, a series of modified adenosine analogs were synthesized and introduced into various RNA oligonucleotide sequences. In this particular technology, more than one modified adenosine analog was introduced at various locations in the desired siRNA oligonucleotide sequence to explore the effects of these modifications on RNA interference activity and off-target protein binding.

Market Applications: Synthesis of chemically modified adenosine analogs is an attractive method of modifying RNA. The new modified adenosines analogs incorporated into siRNA sequences will address the issue of off-target and immunostimulatory effects, and allow for the development of more effective RNA therapeutics.

Features, Benefit & Advantages:
The new derivatives of adenosine nucleoside can be easily converted to a phosphoramidite building block and integrated into any siRNA sequences or siRNA strands.

They are well tolerated in combination with other RNA modifications such as sugar, base or backbone alterations to improve the effectiveness and reduce off-target effects in RNA therapeutics.

Intellectual Property: A provisional patent application has been filed with the U.S. Patent and Trademark Office.

Development Stage: This technology is part of an active and ongoing research program that has been demonstrated to work in proof-of-concept experiments and includes a working prototype. It is available for developmental research support and licensing under either exclusive or non-exclusive terms.

Related Research & Publications:
Dr. Burrows' web page: http://www.chem.utah.edu/directory/faculty/burrows.html

See also U-4599: "Modified Guanine Bases for Controlling Off-Target Effects in RNA Interference"

Keywords: Modified adenosine analogs, phosphoramidite, modified siRNA, siRNA therapeutics, RNA interference.