This project evaluates the potential of utilizing the Antp homeodomain as a non-viral and non- immunogenic vector for gene therapy. Homeodomains represent a double- stranded DNA binding domain in regulatory proteins that determine body patterning during embryogenesis. The Antp homeodomain has the unique property of being able to translocate across the cell membrane and accumulate in the nucleus. The present proposal seeks to exploit these properties to develop the Antp homeodomain into a vector capable of translocating bound, double-stranded DNA into the nucleus. Detailed, 3-dimensional structural information is available for the Antp homeodomain-dsDNA complex which allows one to target critical regions of the molecules for alterations. The following specific aims are planned: 1) to prepare the Antp homeodomain; 2) to examine whether the Antp homeodomain-dsDNA complex or its derivative can be internalized; and 3) to analyze the internalization mechanism of Antp homeodomain- dsDNA.
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