Lentiviral vectors have the unique ability to efficiently transduce non-dividing cells. Since the majority of the cells in the CNS are post mitotic, recombinant Lentiviral vectors can introduce genes in a variety of cell types including neurons and astrocytes. Lentiviral vectors can also be used to knock-down gene expression using RNA interference (RNAi) technology. The vectors can be generate shRNA to specifically compromise the expression of a target gene. Lentiviral vectors can also be designed to regulate gene expression. Adeno associated viral (AAV) vectors can also be used to introduce genes into the CNS. An advantage of AAV is the ability to generate very high titers of recombinant viruses which can allow easier genetic manipulation of higher animals. In some situations, to identify dividing neurons (neurogenesis), retroviral vectors which transduce only dividing cells will be used. Core B will provide higher titer recombinant viruses to all the investigators. Core B will also offer the possibility of training students and post doctoral fellows in the Pi's laboratory to generate viral vectors. Each PI has indicated their expected needs and we have listed them in Core B text.
This program project will find ways to combat the progression of Alzheimer's disease. The gene delivery systems described in Core B are essential to understand how the progression of this disease can be prevented.
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