Engineering of Synthetic Gene
Delivery Systems

Professor Mark E. Davis
Division of Chemistry and Chemical Engineering
California Institute of Technology, Pasadena

DATE: Thursday, Nov 13, 2003
TIME: 4:00 p.m.
PLACE: Engineering II, Room 3361

ABSTRACT

Traditional, small molecule drugs have been derived from natural products (plants, microbes, and marine organisms). With the explosion of genetic information and the creation of nucleic-acid-based therapeutics, new avenues to rational drug design now exist. Unlike small molecule drugs that can passively move into and throughout cells, macromolecular therapeutics must actively be transported. With nucleic-acid-based drugs, the transport must not only be for penetration of the cell membrane but also for the movement to the nucleus of the cell. These demands take drug delivery to a higher level of sophistication by now requiring not only cellular targeting but also intracellular trafficking to specified sub-cellular localizations. Additionally, these new generation of therapeutics should be capable of being: (i) administered repeatedly with little immune response, (ii) produced in large quantities with high reproducibility and acceptable cost, (iii) stable for storage at non-exotic conditions (e.g., room temperature), and (iv) easy to administer to patients.

The thesis of this presentation is that although the delivery of nucleic-acid-based therapeutics is a dauntingly difficult problem, it can be solved by an understanding of the underlying principles of individual steps combined with a systems approach to their integration. Issues that require further understanding for the solution of this outstanding problem will be addressed. Examples of ongoing studies (e.g., materials design and synthesis, colloidal stability at physiological conditions, intracellular trafficking) that attack key points in the overall delivery process will be illustrated to demonstrate how engineering principles can be applied to individual steps and to the integration of a functioning system.