Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), with their abilities to replicate indefinitely and maintain pluripotency, offer tremendous opportunities for the development of novel regenerative medicine-based therapies. iPSC technology, in particular, may provide the means to develop personalized therapeutic strategies in which a patient's own cells might be modified and used to treat their disease without the need for immunosuppression. Patient-derived ESCs and iPSCs will also provide critically important reagents for modeling and studying the biology of various diseases. Despite tremendous recent progress, many significant challenges remain to be addressed before ESCs and iPSCs can be used routinely for therapeutics. For example, methods for generating iPSCs are currently inefficient with considerable room for improvement. In addition, homologous recombination-mediated gene targeting for creating specific mutations works with low efficiency and is difficult to perform, particularly in human ESCs and iPSCs. Lastly, methods for robustly differentiating ESCs and iPSCs into cell types of interest are typically inefficient and yield cells that fail to exhibit all desired characteristics. The goal of this proposal is to employ engineered zinc finger technology to address these major challenges impeding research and therapeutic applications of ESCs and iPSCs. Specifically, this proposal will utilize the PI's expertise in engineered zinc finger technology to address three important challenges for stem cell biology and research: (1) developing more efficient methods for iPSC generation, (2) enabling high efficiency ZFN-induced gene targeting in human ESCs and iPSCs, and (3) creating more efficient methods for differentiating stem cells into desired cell types of interest. Public Health Relevance: This application seeks to address significant challenges that currently limit research and therapeutic applications of human embryonic stem cells a

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
8DP1GM105378-03
Application #
8306207
Study Section
Special Emphasis Panel (ZGM1-NDPA-B (01))
Program Officer
Haynes, Susan R
Project Start
2010-09-30
Project End
2015-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$876,150
Indirect Cost
$381,150
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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