title: Pharmacokinetic considerations in somatic gene therapy.
abstract: It is anticipated that gene therapies will be useful for achieving long durations of action with little temporal fluctuation in the level of the therapeutic gene product, localized effects in specific tissues or cell types, and levels of biological products that can be regulated over time by drugs or physiological events. The effective clinical application of gene therapies will require detailed consideration of the pharmacokinetics of the gene and its gene product. This requires understanding not only the apparent kinetics of the bioactive gene product, but the intrinsic kinetics of each step involved in gene delivery, gene expression and the bioavailability of the gene product. Numerical models are described for three different approaches to gene therapy: (i) those that involve permanent integration of a transgene into the target cell, (ii) those that involve transient residence of the transgene within the cell, and (iii) those that allow control over gene expression by regulatory factors or administered drugs. Experimental studies describing the dynamics and kinetics of DNA in vivo and early pharmacokinetic studies of viral and non-viral systems are reviewed.
authors.affiliation: Massachusetts Institute of Technology, Department of Earth Atmospheric and Planetary Sciences, Cambridge, MA 02139, USA
authors.lastname: Shapiro Ledley T
authors.initials: FD
authors.lastname: Ledley