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DEVELOPMENT OF A TRANSGENIC MOUSE LINE ENGINEERED TO PERMIT SELECTION AND CLONING

Award Number: R43RR031316
ORGANIZATION: NATIONAL CENTER FOR RESEARCH RESOURCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2010
PERIOD OF PERFORMANCE END DATE: 06/30/2011

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DEVELOPMENT OF A TRANSGENIC MOUSE LINE ENGINEERED TO PERMIT SELECTION AND CLONING - DESCRIPTION (provided by applicant): The Applicant proposes an improvement to monoclonal antibody technology through the generation of transgenic mice engineered to facilitate flow cytometric isolation and cloning of specific antigen-reactive plasmacytes. Monoclonal antibodies (mAbs) are arguably the most important biological reagents used in biomedical research, diagnostics, and therapeutics, and the demand for them is increasing exponentially. MAbs are secreted from hybridoma cells that are fusions of antibody-producing lymphocytes (B cells) and immortal myeloma cells. Abeome's patented Direct Selection of Hybridoma (DiSHTM) technology represents a significant improvement to hybridoma technology. Through the use of a novel myeloma parent, genetically engineered for the constitutive expression of transgenic Ig-receptor proteins Ig-alpha and Ig-beta, all of the derived B cell hybridomas express a complete B cell receptor (BCR) complex on the cell surface. Specific hybridomas of interest are subsequently selected and cloned by Fluorescent Activated Cell Sorting (FACS) after labeling the BCR with fluorescent antigen. There remain, however, limitations within hybridoma technology that prevent efficient sampling of the full repertoire of plasmacytes, the lymphocytes producing the highest affinity antibodies. Herein, we are proposing an extension of DiSH technology that will allow the Targeted Selection of Plasmacytes (TSP). The TSP concept is founded on the transgenic expression of Ig-receptor proteins Ig-alpha and Ig-beta in engineered mice. TSP technology will result in surface expression of the BCR complex directly on antibody-secreting plasmacytes in mice, which can then be isolated using FACS based on expression of the BCR complex and its reaction with fluorescently labeled antigen. This Phase I project proposes to establish a colony of TSP transgenic mice, demonstrate expression of the transgene, and show that these mice are immunologically functional and thereby accomplish a major milestone towards a significant commercially feasible improvement in monoclonal antibody technology. PUBLIC HEALTH RELEVANCE: Monoclonal antibodies represent some of the most successful research and diagnostic tools available to scientists and clinicians. More importantly, their high specificity and sensitivity, coupled with favorable pharmacokinetics and safety, make them highly attractive therapeutic agents. The Applicant proposes the generation of transgenic mice that would greatly facilitate the isolation of antigen-specific plasma cells directly from immunized animals, thereby improving the speed and efficiency of obtaining monoclonal antibodies. The proposed project represents a major milestone towards the ultimate goal of generating transgenic mice that eliminate the requirement for the currently required myeloma-B cell fusion step.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2010 ( Subtotal = $133,995 )
2010	2010	ABEOME CORPORATION	111 RIVERBEND ROAD	ATHENS	GA	30605	CLARKE	USA	National Center for Research Resources	000	1	7/9/2010	NEW	$133,995
														Subtotal = $133,995

Grand Total All Awards = $133,995

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DEVELOPMENT OF A TRANSGENIC MOUSE LINE ENGINEERED TO PERMIT SELECTION AND CLONING

Award Number: R43RR031316

ORGANIZATION: NATIONAL CENTER FOR RESEARCH RESOURCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/15/2010

PERIOD OF PERFORMANCE END DATE: 06/30/2011

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