Application of gene therapy to acute inflammatory diseases

The application of gene therapy to acute inflammation has not received as m uch research attention as has the treatment of genetically-based diseases, cancer, and viral infections. However, gene therapy as a drug delivery syst em offers several theoretical and practical advantages over current protein delivery systems. These include the ability to target therapies to individ ual tissues or cell types, to locally produce proteins that can act intrace llularly or in an autocrine, juxtacrine, or paracrine fashion, and to susta in new protein synthesis for periods up to several weeks after a single adm inistration. Although retrovirus, herpes simplex, and adeno-associated viru s have been proposed for gene therapy in cancer and in genetic diseases, no nviral and adenovirus approaches appear most applicable as drug delivery sy stems due to their rapid onset and short duration of transgene expression. The relative modest transduction efficiencies obtained at present with nonv iral approaches, and the inherent inflammatory properties of first-generati on adenovirus constructs, however, have limited their usefulness to date. T he present review discusses the theoretical and practical benefits of speci fic gene therapy approaches for the treatment of acute inflammatory disease s, as well as our experiences with liposome:plasmid DNA and adenovirus-base d approaches. Although a number of technical and theoretical hurdles remain before it can be evaluated in humans with acute inflammation, gene therapy offers a novel approach for the treatment of acute inflammation, and will likely enter the armamentarium of critical care physicians in the near futu re.