Molecular Light Switch for Controlled Gene Expression

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$298,430.00
Award Year:
2013
Program:
SBIR
Phase:
Phase I
Contract:
1R43GM105182-01
Award Id:
n/a
Agency Tracking Number:
R43GM105182
Solicitation Year:
2013
Solicitation Topic Code:
NIGMS
Solicitation Number:
PA12-088
Small Business Information
2905 Parmenter St., MIDDLETON, WI, -
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
19710669
Principal Investigator:
MICHELEAULDRIDGE
(608) 203-9516
mauldridge@lucigen.com
Business Contact:
MICHELEAULDRIDGE
(608) 831-9011
mauldridge@lucigen.com
Research Institute:
Stub




Abstract
DESCRIPTION (provided by applicant): Experimental manipulation of gene expression is a widely used technique that is crucial to much of modern biomedical research. The ability to control the timing and expression level of recombinant genes is central to the production of recombinant protein for basic research as well as for the synthesis of biological pharmaceuticals. Commercially available systems for controlling gene expression in mammalian cells, whether in laboratory cultures or in whole animals, are dependent on the application of small molecule drugs to induce or repress transcription. These systems suffer from several limitations, including toxicity, off-target effects, lack of precision in relation to timing and loation, and reversibility of induction. Moreover, the cost of the effector drug and necessary drug-free media can be burdensome. New technologies are needed to overcome these limitations. The current project aims to develop a new system for inducible control of gene expression using long-wavelength (700-750 nm) light. In addition to avoiding the side effects and costs associated with drug-based systems, light-inducible control offers the advantages of precise spatial and temporal targeting of individual tissues and cells. Light also avoids the uptake and transport requirements inherent in small molecule-based inducers. Our proposed strategy will exploit a photoreceptor class that is naturally responsive to long-wavelength light, and convert it into a molecular light switch that controls transcription of target genes. The selected photoreceptor is also naturally photoreversible enabling the engineered transcriptional switch to exert an unprecedented level of transcriptional control. Successful development of this system has the potential notonly to revolutionize inducible gene expression in mammalian cell culture, but is also likely to advance the study of transgenic expression in whole animals and the development of novel genetic therapies. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Technologies enabling control of gene expression, whether in laboratory cultures or in whole organisms, play a critical role in public health. Controlled gene expression permits production of proteins for research and therapeutics, but it is alsocrucial to basic research on early cellular responses. This project aims to develop a new technology to exploit light, at the upper limit of the visible range, for the precise experimental control over gne expression, circumventing limitations of current systems that require the application of small-molecule drugs.

* information listed above is at the time of submission.

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