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TRANSKARYOTIC THERAPIES, INC. REPORTS FASTER SYSTEM TO ISOLATE GENES ASSOCIATED WITH COMMON DISEASES

 CAMBRIDGE, Mass., Sept. 20 /PRNewswire/ -- Scientists at Transkaryotic Therapies, Inc. (TKT) reported this week that they have developed a system to isolate genes associated with common diseases that is 10-to-100 times faster than is possible with current technologies.
 Allan Miller and colleagues describe the system in a report published in the current issue of the Proceedings of tje National Academy of Sciences entitled, "Recombination walking: Genetic selection of clones from pooled libraries of yeast artificial chromosomes by homologous recombination."
 "Recombination walking is a biological approach to isolating genes," said Miller. "Instead of having scientists sift by hand through vast amounts of genetic information to find a DNA fragment of interest, this technology programs yeast cells to do the work more rapidly, efficiently, and cost-effectively."
 Over the past decade, significant progress has been made in determining the approximate chromosomal location of a large number of disease genes including those associated with diabetes, Alzheimer disease, asthma, and various forms of cancer. Up until now, the precise localization of these genes has relied on brute force techniques that, although successfully applied to the isolation of rare disease genes, have not proven efficient for the isolation of common disease genes. Using TKT's technology, this precise localization is performed by aligning yeast artificial chromosomes -- and the yeast themselves have been engineered to perform the aligning. The process is based on homologous recombination, a natural biological phenomena that allows cells to pick out sets of related DNA sequences. In a sense, DNA fragments near the gene of interest resembles pieces of a complex puzzle -- using homologous recombination, yeast cells assemble the puzzle so that the gene can be isolated.
 TKT's system for chromosome walking represents a major advance in efficiency over state-of-the-art technology and is focused on the isolation of genes associated with common diseases. TKT's technology is particularly applicable in this setting because the majority of common medical disorders are not due to a single gene defect but to a complex series of interactions involving multiple genes. TKT's initial disease targets are diabetes, Alzheimer disease, and malignant melanoma. The company is collaborating with scientists at the Bowman-Gray School of Medicine to isolate genes associated with adult onset diabetes and plans to enter into additional collaborations when appropriate.
 "For common human diseases, the ability to assemble detailed maps of a number of chromosomal locations is an absolute requirement, and TKT's proprietary technology is so efficient as to make the cloning of the genes associated with common diseases both practical and economical," said Douglas Treco, TKT's vice president of research.
 TKT plans to utilize genes isolated through use of recombination walking in three ways:
 -- The identification of genes causing common diseases will provide a framework for advances in pharmacology, both through the production of the protein they encode (and appropriate analogs), and the identification of compounds that affect the in vivo expression of the genes themselves.
 -- The identified genes will lead to early and reliable diagnostics, resulting in some cases in more effective pharmacological interventions. New diagnostic tools will also lead to disease prevention, since in many cases lifestyle and nutrition are major factors in disease progression in susceptible individuals.
 -- A subset of the newly isolated disease genes will be utilized in the company's gene therapy program, further strengthening TKT's proprietary position in this field.
 Recombination walking is complementary to the genome mapping and sequencing work being formed as part of the human genome project. One of the initial goals of this government-sponsored project is to develop a coarse map of the human genome, with a long-term goal of sequencing the entire genome. Recombination walking would allow the conversion of this coarse map into a detailed map that would then allow efficient sequencing. Similarly, TKT's technology is distinct from random DNA-sequencing strategies that are being developed. Such strategies are focused on sequencing random pieces of DNA in the hopes of identifying every human gene. In contrast, recombination walking is focused on the isolation of a subset of human genes -- those causing major common diseases.
 Transkaryotic Therapies, Inc. is dedicated to the development and commercialization of non-viral gene therapy products for the long-term treatment of a broad range of human diseases. TKT also is developing powerful new technologies which will enable the surgically precise modification of human chromosomes, and the rapid, cost-effective isolation of genes responsible for common diseases.
 -0- 9/20/93
 /NOTE TO EDITORS: Artwork (Macintosh generated) is available for your review in support of this story./
 /CONTACT: Lorraine Ruff of Stoorza, Ziegaus & Metzger, Inc., 619-236-1332, or home, 619-755-5610/


CO: Transkaryotic Therapies, Inc. ST: Massachusetts IN: MTC SU: PDT

TW -- NY020A -- 3652 09/20/93 12:00 EDT
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Date:Sep 20, 1993
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