In-vivo miRNA Detection Using Structurally Interacting RNA (sxRNA)

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$293,557.00
Award Year:
2011
Program:
STTR
Phase:
Phase I
Contract:
1R41GM097811-01A1
Award Id:
n/a
Agency Tracking Number:
R41GM097811
Solicitation Year:
2011
Solicitation Topic Code:
NIGMS
Solicitation Number:
PA10-051
Small Business Information
170 CHESTNUT ST, ALBANY, NY, 12210-1906
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
808416700
Principal Investigator:
SCOTT TENENBAUM
(518) 437-8871
stenenbaum@albany.edu
Business Contact:
EDWARD EVELETH
(518) 331-1133
ted.eveleth@hocuslocus.com
Research Institution:
STATE UNIVERSITY OF NEW YORK, ALBANY

STATE UNIVERSITY OF NEW YORK
STATE UNIVERSITY PLAZA ALBANY, NY 12246
ALBANY, NY, 12246-
() -
Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): We propose developing a trans-molecular RNA-switch for scientists to measure miRNA activity in-vivo. While there are numerous methods to quantify miRNAs in vitro, we are not aware of any method that allows for in vivo analysis. The ability to observe specific miRNA generation in living single cells without requiring the destruction of the cell would be a significant tool. We are pioneering an RNA-based switch technology called structurally interacting RNAs (sxRNA) whichutilizes post-transcriptional gene regulation as a reporter for miRNA detection. Normally, RNA-binding proteins (RBP) associate with a 3' stem-loop structure to facilitate translation of an upstream coding region by as much as an order of magnitude. It ispossible to modify the mRNA to modulate translation of the reporter gene by controlling the binding of RBP. This is accomplished by altering the natural stem-loop structure so that it does not form unless an additional RNA, such as a miRNA, binds and stabilizes the functional structure by base- pairing with the flanking regions of the custom designed stem-loop. Our goal with this proposal is first to evaluate the switch mechanism in-vitro and measure the specificity of interaction and signal strength possible. Secondly, we will measure the effect on translation and determine whether this switching mechanism is effective in a cell. Success at the product level using sxRNA as a diagnostic tool should ideally position the technology for additional uses. It could be effective anywhere that miRNA expression levels are an indicator of disease, cell or tissue type, or condition. sxRNA could be an RNA-based alternative to gene therapy for protein deficiency diseases, such as cystic fibrosis, or a cancer therapy.PUBLIC HEALTH RELEVANCE: While there are numerous methods to quantify miRNAs in vitro, we are not aware of any method that allows for in vivo analysis. The ability to observe specific miRNA generation in living single cells without requiring the destruction of the cell would be a significant tool. For example, stem cell researchers could ensure stem cells had not differentiated by in-vivo detection of miRNAs that are preferentially expressed during differentiation.

* information listed above is at the time of submission.

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