There is presently a great deal of interest in developing efficient, nontoxic, cell-specific gene transfer vectors. Specifically, there has been a focused interest in the development of nonviral vectors which have several advantages over their viral counterparts in that they cannot reconvert, they can be designed to carry a variety of genetic payloads, and they can be modified with target vectors without disruption of activity. Recent work in collaboration with the University of Michigan Medical School has shown that STARBURST dendrimer polymers (STARBURST is a trademark of Dendritech, Inc.) can be used to mediate highly efficient genetic material of any size or form into cells. In this proposal, this information will be utilized to (l) design and develop new Starburst dendrimer polymers for improving the efficiency of gene transfer into cells (2) make conjugates of dendrimers with antibodies that would bind and direct genetic material specifically to adenocarcinoma cells that express CEA, and (3) examine the efficiency and specificity of these different polymer conjugates for transferring DNA into adenocarcinoma cell lines that express different levels of CEA. This will develop the basis for a vector to deliver therapeutic forms of nucleic acid to adenocarcinoma cells.
This project describes the initial phase of the development of a site-specific gene therapeutic agent against colon cancer and malignant neoplasms of the gastrointestinal tract.
| Bielinska, A U; Kukowska-Latallo, J F; Baker Jr, J R (1997) The interaction of plasmid DNA with polyamidoamine dendrimers: mechanism of complex formation and analysis of alterations induced in nuclease sensitivity and transcriptional activity of the complexed DNA. Biochim Biophys Acta 1353:180-90 |
| Kukowska-Latallo, J F; Bielinska, A U; Johnson, J et al. (1996) Efficient transfer of genetic material into mammalian cells using Starburst polyamidoamine dendrimers. Proc Natl Acad Sci U S A 93:4897-902 |
