BPEC Strategic Plan continued

Example clinical applications for Category II include therapeutics for cancer (i.e., liver cancer, breast cancer, brain cancer, and prostate cancer) as well as proteins secreted into the circulation (i.e., clotting factors for hemophilia and antiproteases for emphysema). In this category, the knowledge base required to build appropriate delivery vehicles is quite strong but must be translated into actual technologies and ultimate targeted delivery vehicles as engineered systems. The critical issue is how to target viral or synthetic vectors to precisely the correct cell type in a potentially repeatable manner, with vector testing for delivery selectivity and efficiency done as predictively as possible.

Category III comprises therapeutics involving delivery where the cell type in which the transgene is expressed is crucial, the expression level and its regulation may be important the the longevity or repeatability of expression is essential. Example clinical applications for Category III include therapeutics for genetic diseases such as sickle cell anemia, thalassemia, cystic fibrosis, muscular dystrophy, Tay-Sachs, and Gaucher's. Because of the crucial need for expression longeivty in a differentiated cell type of limited lifespan, delivering the transgene in the proper upstream stem cell is the only promising approach.

For development of effective stem cell gene delivery vectors, the most difficult unsolved problem is the inability to generate sufficiently great numbers of the proper genetically engineered stem cells in culture for reimplantation.

 

Solving this problem requires major advances even in the knowledge base for regulation of stem cell proliferation and differentiation, in order to create a technology base for stem cell generation and expansion.

Thus, we see a critical role for BPEC in elucidating basic understanding of how stem cells are controlled, then translating this knowledge into bioreactor technology for carrying out stem cell expansion. The ultimate engineered systems would be genetically engineered stem cells, generated and expanded in culture bioreactors and transduced by viral vectors, ready for transfer to partners who would accomplish the host reimplantations.

In our Project Area A (Figure 5.2), we are tackling blood cell genetic diseases as specific endpoint applications, so are focusing on basic biology and bioreactor technology issues for hematopoietic stem cells and their potential generation from embryonic stem cells. The knowledge based for viral vectors capable of long-term expression is progressing well in a number of laboratories around the country as well as our own, so we may add a new collaboration combining effective viral vectors with out stem cell biotechnology in the near future.

We believe we have defined and motivated a very clear and compelling Vision for our BPEC ERC - to create engineered systems of selective gene delivery vehicles for disease applications in liver cancer and genetic diseases of blood cells - Project Area A and Project Area B (Figure 5.3) in our BPEC Strategic Plan