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Enabling Technologies for Embryonic Stem Cell Functional Genomics

Status: 
Past
Competition: 
New Technology Development
Sector: 
Health
Genome Centre(s):
Genome Prairie
Project Leader(s):
Geoff Hicks (University of Manitoba)
Fiscal Year Project Launched: 
2007-2008
Project Description: 

Embryonic stem (ES) cells have played an indispensable role in the discovery of the function of human disease genes and in creating mouse models of human disease. The “knockout” mouse, for example, allows researchers to identify gene function by examining the effect of gene alteration in ES cells and in mice derived from them. This powerful approach allows scientists to create animal models of disease, which can be used to study the causes of human disease and potential treatment or intervention strategies. With this proven and very powerful discovery tool, the International Knockout Mouse Consortium has established an integrated $100M worldwide effort that will rapidly and efficiently generate designed mutations in every gene in the mouse genome and make them freely available to all biomedical researchers. This resource is expected to have a wide reaching and significant impact across diverse scientific disciplines of a magnitude similar to those realized by the sequencing of the Human Genome.

ES cells have many other applications. Particularly with human ES cells now coming on line, ES cells have the potential to transform our knowledge of human disease and development and give rise to new classes of therapeutic agents – from novel drugs to cell-based therapies. Such studies are done only in cells and are approved by a national stem cell regulatory board to make certain legal and ethical aspects of using human stem cells are taken into consideration by an independent body.

To ensure Canada is strategically positioned to take full advantage of mouse and human ES cell resources, the scientists in this proposal identify several key barriers in the current state of ES cell technology and propose to develop novel technologies to overcome these barriers. The proposed technologies in this project will be developed using mouse ES cells, but can be applied by others to any model cell system. Each cutting edge technology is recently established in principle by the respective PIs and the current project application will allow a three-prong implementation strategy: development of the technology, validation of the technology, and delivery of the technology in a form that is readily accessible and immediately usable by the scientific community without specialized training. These enabling technologies are expected to significantly impact biomedical disease-focus research programs and biotech companies in Canada and thereby increase the rate at which new medical discoveries are moved into health care delivery.

Outcomes: 

We have developed novel plasmid recombineering approaches which can be used by the scientific community to develop recombinant plasmids for the biotechnology and biomedical research sectors. We devised a new counter-selection marker and a method using the new marker which we named “Blue Tag”. The new method can replace the existing methods with greatly improved efficiency for isolation of desired recombinants. It can be used for modification of DNA sequence (insertion, replacement, deletion) without leaving exogenous sequence behind.

We also developed novel plasmid shuffling techniques which can be used to generate new plasmids without the need to use restriction enzymes and ligases.

We will continue to approach Canadian academic researchers and biopharmaceutical companies who are potential users of mouse embryonic stem cells in their research to understand the genetic basis of disease, discover and validate new targets, and accelerate the pathway to commercialization. We will use formal and informal business development channels and strategic marketing tools such as a brochure, website, and slide presentations tailored to specific audiences (academia, biopharmaceutical companies and venture capital firms). Publication regarding the development of the technologies will be sought in high impact international journals.

The project technologies will considerably enhance the availabilities of knockout mouse resources and enable the functional analysis of the mammalian genome. This will significantly impact biomedical disease-focus research programs and biotech companies in Canada and thereby increase the rate at which new medical discoveries are moved into health care delivery and enhance the well-being of Canadians. The project will have wide reaching and significant impact across broadly diverse scientific disciplines and provide Canadians with significant competitive advantage. We anticipate the technology developed through the project will lead to employment opportunities in Academia and in the Biotech sector.

The technologies will be made freely available and will be available to Genome Canada funded platforms and other not-for-profit academic users through a no-cost, non-exclusive license. The technologies will be available to the private for-profit sector for a fee. The technology transfer offices of the participating institutions will manage commercialization and IP aspects of the technologies developed in the project. Meetings will be held regularly between Technology Team members and the technology transfer offices of the relevant institutions to facilitate delivery of project technologies to end-users in a timely and efficient manner.