Molecular Engineering of Stem Cell and Gene Therapies
Schaffer, David V.
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There are numerous diseases for which there is still no cure, and new molecular therapies based on stem cells and gene delivery have significant therapeutic potential. Before these approaches can succeed, however, a number of fundamental challenges must be overcome, particularly in the nervous system, our tissue of interest. Stem cells have significant potential for treating a wide variety of disorders, and their successful integration into such therapies will hinge upon three critical steps: their expansion without differentiation (i.e., self-renewal), their differentiation into specific cell types, and their functional integration into existing tissue. Precisely controlling each of these steps will be essential to maximize their therapeutic efficacy, as well as minimize potential side effects. We combine experimental and computational approaches to understand basic mechanisms by which microenvironmental signals regulate of stem cell fate choice, including neural stem and human embryonic stem cells. Furthermore, we have applied this basic information towards the engineering of synthetic, biomaterial based microenvironments for the expansion and differentiation of stem cells. Gene therapy, introduction of genetic material to the cells of a patient for therapeutic benefit, has enormous potential to synergize with stem cells to repair damaged tissue through the delivery of genes to control stem cell function. However, the vehicles or vectors that deliver therapeutic nucleic acids require highly challenging engineering for enhanced efficiency and safety. Our efforts are focused on engineering vehicles based on viruses at the molecular level to overcome the common dilemma faced by all: they did not evolve in nature to perform the therapeutic endeavors we ask of them. Specifically, we are applying directed evolution approaches to fundamentally change the properties of viruses at the molecular level. We hope that these capabilities can be combined to regenerate tissue from the effects of devastating, chronic disorders, such as Alzheimer’s, Parkinson’s, and Lou Gehrig’s Diseases.