Ribozyme can be used to repair messenger RNA agrees with the panel that the field "unfortunately has been dormant." He also backs the panel's recommendations of more R&D funding, clearer regulatory guidelines, and a federal product liability law. However, Djerassi tells C&EN, the report overpromises on the prospects for new contraceptives in the next 10 years, and he is not hopeful about a pickup in the pace of development. Drug firms have little economic incentive to develop contraceptives, he believes. Indeed, he adds, the more a new contraceptive is cost-effective and a "social bargain," the less a drug company will be interested in it. So, he stresses, new incentives must be found. Stu Borman
mRNA containing defect (D)
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Ribozyme with corrected (C) RNA segment attached
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at many other sites. Reaction efficiency must be improved. And in common with all gene therapy approaches, better techniques are needed to deliver the engineered ribozymes into the cells where they are to function. Rebecca Rawls
Ribozyme
Biotech acquisitions boost Genzyme, Sandoz I Ribozyme-catalyzed I cleavage and ligation
Two very different companies, Genzyme and Sandoz, plan biotechnology— C i related acquisitions that will boost their Corrected mRNA capabilities—Genzyme in marketing Adapted from Jones et. al., Nat. Med, 2, 643 (1996) and Sandoz in drug discovery. Genzyme, a Cambridge, Mass.-based biopharmaceutical company, will spend at the RNA level/' Sullenger explains. about $250 million in cash to acquire Splicing ribozyme can He notes that the cells of higher organ- Deknatel Snowden Pencer (DSP), a priincluding humans, routinely re- vately held surgical products firm 'edit' mammalian RNA isms, vise the RNA transcript many times af- based in Fall River, Mass. DSP sales for ter it is produced as a complementary the fiscal year ending last Sept. 30 toIn a novel approach to gene therapy, re- copy of the information stored in the taled $95.3 million. searchers at Duke University Medical gene and before it serves as the temMost important to Genzyme is DSP's Center have shown that ribozymes can plate for synthesizing a new protein. 70-person U.S. and European sales "edit" genetic information encoded in "We want to take therapeutic advan- force. Genzyme has been developing messenger RNA molecules inside mam- tage of what cells are already doing." film, gel, and coating products demalian cells. If further development is Two years ago, while he was a post- signed to reduce adhesions in surgical successful, the technique could, in effect, doctoral researcher at the University of procedures. Earlier this year, a Food & bypass a defective gene and instead cor- Colorado, Boulder, Sullenger and chem- Drug Administration advisory panel rect the RNA blueprint the gene produc- istry professor Thomas R. Cech showed recommended approval to market the es to direct protein synthesis. that a splicing ribozyme from a protozo- first of these products—a "bioresorbRibozymes are RNA segments that an could be engineered to splice togeth- able" membrane already sold in parts catalyze reactions within cells. Because er two RNA segments in the test tube or of Europe. they selectively bind and react with oth- in bacterial cells so the joined segments "The acquisition of DSP will create a er RNA segments, they have drawn at- would direct synthesis of the correct platform for building a specialty surgery tention as potential tools that could pro- protein. The Duke researchers have tak- business and will allow us to rapidly estect against viral infection by cleaving en the work a step closer to medical ap- tablish ourselves in the surgical marketand destroying an invading virus's plications by showing that the technique place," says Henri A. Termeer, GenRNA. Clinical trials are now testing the works in mammalian cells. zyme's chairman and chief executive ofpotential of several modified ribozymes One advantage of this approach over ficer. Genzyme will keep DSP's three to protect against HIV infection. "conventional" gene therapy—in which U.S. facilities and 585 employees. WilBut the Duke team's approach is quite a repaired gene is inserted into the gene liam C. Dow, DSP chairman, president, different. Assistant professor of surgery pool—is that the gene stays in its natural and CEO, will become president of Genand genetics Bruce A. Sullenger, re- environment. This means no disturbance zyme's surgical products business unit. search assistant Joshua T. Jones, and to all the things that regulate its expresGenzyme is among the top biopharpostdoctoral fellow Seong-Wook Lee sion, explain Nava Sarver and Scott maceutical companies and markets two modified a ribozyme from a different Cairns of the National Institute of Aller- major therapeutic products. Its total revclass than those that cleave viral RNA gy & Infectious Diseases, Bethesda, Md., enues last year were $379 million, with [Nat. Med., 2, 643 (1996)]. Theirs is a in a commentary in the same issue of net earnings of about $58 million before splicing ribozyme; it cuts RNA at a spe- Nature Medicine. Getting well-regulatedspecial acquisition-related charges. cific location and attaches a new piece of gene expression from repaired genes has It also operates a division that is deRNA in place of the old one. Thus, in been extremely difficult, they note. veloping tissue repair technology, and principle, the ribozyme can "repair" a Although splicing ribozymes show it runs a genetic diagnostic services defective RNA blueprint by cutting off promise for gene therapy, several major business. Late last year and early this the portion containing the defect and re- problems remain. The ribozyme's target- year, it acquired two genetic testing placing it with a correct segment. ing is not yet specific enough: In this ex- firms—IG Laboratories of Framing"We're trying to develop ribozymes periment, the ribozymes attached a new ham, Mass., and Genetrix of Phoenix. that can change the genetic instructions end segment not only where needed but And Genzyme holds a 48% stake in JUNE 3,1996 C&EN
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