GENETICALLY ENGINEERED ENTEROENDOCRINE CELLS FOR TREATING GLUCOSE-RELATED METABOLIC DISORDERS

摘要

Methods and compositions for restoration of regulated insulin release in response to blood glucose levels in an individual in need thereof are disclosed. A recombinant adeno-associated virus expression vector expressing preproinsulin or insulin is used for selective transduction of enteroendocrine cells. Cells can be transfected with vectors where the genes of interest are under the control of tissue-specific promoters. Other appropriate enhancers or transcriptional regulators may be included in the vector to modulate expression. Cells can be transduced in vivo or manipulated ex vivo and transplanted into an individual in need of treatment. A selection gene or reporter gene can optionally be included in the vector for selection of transduced cells after expression of the vector. Genes encoding luminescent markers can optionally be included in the vector to allow for selection of transduced cells using fluorescence-based selection procedures.