Optimization of localized expression from lentiviral vectors for use in gene transfer to the airway epithelia
Gene transfer to the airway epithelia is a major goal in therapeutic medicine for the treatment of Cystic Fibrosis. One vehicle used to achieve this goal is the viral vector. Lentivirus is a member of the Retrovirus family. They offer many advantages over other viral vectors including the ability to persist through integration into the host genome and the ability to transduce slowly-dividing cell types (such as those found in the airway epithelia). Our lab has worked on optimizing the Feline Immunodeficiency Virus (FIV) vector. Work has included pseudotyping the virus to achieve greater tropism, and thus transduction efficiency, for the airway and inclusion of cis-acting elements in the transgene cassette to confer greater transgene expression. One of the aims of the project on which I am working involves the use of various tissue-specific promoters within the context of FIV to confer persistent and sufficient transgene expression in the airway. Another aim is to direct integration to a specific site (or sites) in the genome to achieve greater safety by avoiding insertional mutagenesis caused by vector integration.
