8 ❖ Speakers Gene Therapy

Speakers •

R. Michael Blaese, M.D.

Chief Scientific OfficerKimeragen, Inc.300 Pheasant RunNewtown, PA 18940United States

Since the early 1980s, Dr. Blaese’s work has centered ondevising techniques that exploit the vast and unique store ofinformation contained in human and non-human genes fortreatment of human disease. His earlier NIH work included theinitial pioneering ADA T-cell trial with partner French Anderson,the ADA cord blood stem cell clinical study with Donald Kohn,and the HSV-tk brain tumor trial with Ram, Culver, andOldfield. With Lane, Walker, and Morgan, he is involved in along-term project to develop gene therapy for AIDS, testingvarious T cell gene-modifications using pairs of identical twinsthat are discordant for HIV infection. His laboratory also intro-duced replicating viral vectors that spread transgenes in cancermore efficiently than disabled vectors and also directly lyse thetumor cells they infect. Continuing at NIH as an adjunct investi-gator, Dr. Blaese retired from his full-time position in January1999 to join Kimeragen as Chief Scientific Officer. Kimeragen’sproprietary technology employing chimeric RNA-DNA oligonu-cleotide-directed gene repair represents a quantum advance ingene therapy technology, and Dr. Blaese directs the company’sresearch effort and its development of clinical applications andproducts. During his career he has authored over 320 researchreports, articles, chapters, and textbook contributions.

Challenges of Genetic Disease: GeneAddition or Gene Repair

A decade after the initial use of viral-mediated gene transfer inhuman clinical trials, the hoped for goal of harnessing the vastinformation contained in our genes for effective therapy of abroad array of conditions has not yet been achieved. Especiallyfor treatment of genetic diseases, progress using the generalapproach of “gene addition” has been agonizingly slow. Thislimited progress has been in part due to inefficient gene deliv-ery, particularly for in vivo applications. Even in those systemswhere gene delivery is satisfactory, cell-to-cell variability intransgene expression as a result of random integration, theinability to reverse “dominant negative” gene disorders, and thelack of systems to provide normal “physiologic” regulation ofthe inserted transgene have kept most of the 3000+ monogenicdisease targets off the lists of current candidate disorders. Analternative strategy for treatment of genetic diseases, gene repairhas recently shown promise in both tissue culture and animalmodel studies. Chimeric oligonucleotides consisting of bothDNA and RNA (chimeraplasts) are able to specifically and per-manently change genomic DNA sequences. Using the cell’sown DNA mismatch repair machinery, chimeraplasty has beenshown to be active in bacteria, yeast, insects, plants, rodent, andhuman cells to either correct genetic defects or to disable nor-mal gene functions. The properties of this gene repair systemwill be contrasted with technologies for gene addition as poten-tial molecular tools for human therapy.

© 1999 Nature America Inc. • http://biotech.nature.com©

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