My research involves the synthesis and development of
lipids and polymers as agents for transporting genes into mammalian
cells. The insertion of foreign genes into cells has great potential in
molecular biology and medicine. Graduate students in my group spend much
of their time synthesizing novel delivery agents. As new delivery
vectors are prepared, the research focus shifts to cell culture
experimentation involving a variety of assays, biophysical measurements
and issues of formulation.
The use of cationic lipids as vehicles for gene
transfer is one of our principal research interests. Cationic lipids
spontaneously associate with DNA on simple mixing. The resultant
charge-affinity complex is termed a lipoplex and it consists of DNA that
is completely surrounded by lipid bilayers. The addition of lipoplexes
to cells results in their rapid cellular uptake, thus facilitating entry
of the bound DNA into these cells. Ultimately, a small portion of the
internalized DNA finds its way to the nucleus. In this way, DNA can be
used as a pharmaceutical agent. Those cells that internalized the
lipoplexes now have the ability to express an encoded therapeutic
protein, such as insulin for example.
The chemical structure of cationic lipids determines
to a great extent the efficiency of the overall gene transfer and
expression process. For this reason, we put much effort into designing
and synthesizing new cationic materials, including cationic and
biodegradable polymers, for use in DNA delivery applications.
