Title:
GLYCINE RIBOSWITCHES, METHODS FOR THEIR USE, AND COMPOSITIONS FOR USE WITH GLYCINE RIBOSWITCHES
Document Type and Number:
WIPO Patent Application WO2006042143
Kind Code:
A3
Abstract:
It has been discovered that certain natural mRNAs serve as metabolite-sensitive genetic switches wherein the RNA directly binds a small organic molecule. This binding process changes the conformation of the mRNA, which causes a change in gene expression by a variety of different mechanisms. Modified versions of these natural "riboswitches" (created by using various nucleic acid engineering strategies) can be employed as designer genetic switches that are controlled by specific effector compounds. Such effector compounds that activate a riboswitch are referred to herein as trigger molecules. The natural switches are targets for antibiotics and other small molecule therapies. In addition, the architecture of riboswitches allows actual pieces of the natural switches to be used to construct new non-immunogenic genetic control elements, for example the aptamer (molecular recognition) domain can be swapped with other non-natural aptamers (or otherwise modified) such that the new recognition domain causes genetic modulation with user-defined effector compounds. The changed switches become part of a therapy regimen-turning on, or off, or regulating protein synthesis. Newly constructed genetic regulation networks can be applied in such areas as living biosensors, metabolic engineering of organisms, and in advanced forms of gene therapy treatments.
Inventors:
BREAKER RONALD R (US)
BARRICK JEFFREY (US)
MANDAL MAUMITA (US)
BARRICK JEFFREY (US)
MANDAL MAUMITA (US)
Application Number:
PCT/US2005/036218
Publication Date:
July 13, 2006
Filing Date:
October 07, 2005
Export Citation:
Assignee:
UNIV YALE (US)
BREAKER RONALD R (US)
BARRICK JEFFREY (US)
MANDAL MAUMITA (US)
BREAKER RONALD R (US)
BARRICK JEFFREY (US)
MANDAL MAUMITA (US)
International Classes:
C12Q1/68; C07H21/04
Other References:
MANDAL ET AL.: "A Glycine-Dependent Riboswitch That Uses Cooperative Binding to Control Gene Expression", SCIENCE, vol. 306, no. 5694, 8 October 2004 (2004-10-08), pages 275 - 279, XP003000209
SUDARSAN ET AL.: "Metabolite-binding RNA domains are present in the genes of eukaryotes", RNA, vol. 9, no. 6, June 2003 (2003-06-01), pages 644 - 647, XP003000210
VITRESCHAK ET AL.: "Riboswitches: the oldest mechanism for the regulation of gene expression?", TRENDS IN GENETICS, vol. 20, no. 1, January 2004 (2004-01-01), pages 44 - 50, XP004481965
TUCKER ET AL.: "Riboswitches as versatile gene control elements", CURRENT OPINION IN STRUCTURAL BIOLOGY, vol. 15, 2005, pages 342 - 348, XP004998057
SUDARSAN ET AL.: "Metabolite-binding RNA domains are present in the genes of eukaryotes", RNA, vol. 9, no. 6, June 2003 (2003-06-01), pages 644 - 647, XP003000210
VITRESCHAK ET AL.: "Riboswitches: the oldest mechanism for the regulation of gene expression?", TRENDS IN GENETICS, vol. 20, no. 1, January 2004 (2004-01-01), pages 44 - 50, XP004481965
TUCKER ET AL.: "Riboswitches as versatile gene control elements", CURRENT OPINION IN STRUCTURAL BIOLOGY, vol. 15, 2005, pages 342 - 348, XP004998057
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