This Small Business Innovation Research (SBIR) Phase I research project aims to improve the frequency of homologous recombination by increasing the number of targeting vector molecules that reach the nucleus. The technology is based on constructing targeting vectors that have proteins involved in nuclear translocation attached. Recombination events that can target an exogenous DNA constructs to a particular gene are relatively rare due to a variety of reasons, one of the most important of which is the low frequency of transport across the nuclear membrane. Thus, an approach based on the use of members of a cell's own nuclear translocation machinery is likely to improve the odds of successful recombination events. Important therapeutic modalities such as gene therapy are dependent upon the efficient targeting of specific chromosomal loci. Development of methodologies that enhance nuclear targeting would improve the odds of successful recombination events and as such would not only be important for gene therapy, but also for the creation of novel animal models, which is also dependant on homologous recombination.
