Ribozymes cleave AIDS virus genetic material - C&EN Global

The work could lead to use of ribozymes as therapeutic agents against HIV, the virus that causes AIDS, or eventually in anti-HIV gene therapy. The res...
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News of the Week anese and U.S. research from "the harsh decision/' made "without any consultation with Japanese and oth­ er international partners." Along with abrupt U.S. actions on other international projects, the decision heightens concern abroad that the U.S. is "an unreliable partner for international collaborations." DOE officials justify the closure on economic grounds, citing opera­ tional costs of $100 million to $115 million a year. And at a House Ap­ propriations subcommittee hearing last week, Secretary of Energy James D. Watkins explained that "its con­ t i n u e d operation w o u l d require identification of a long-term mis­ sion, which is not apparent. We ex­ amined various missions, including plutonium-238 production [for use as a power and heat source in space and terrestrial programs], but none of these were deemed to be a costeffective use." DOE planned to start closeout ac­ tivities on April 1. However, two House committees have rejected its request to reprogram some fiscal 1990 funds to start the shutdown, delaying any closeout action until October. For fiscal 1991, the pro­ posed, budget only provides closeout funding. FFTF backers are now seek­ ing funding from other federal pro­ grams, and from industry, Washing­ ton state, and foreign sources. Richard Seltzer

Indian court set to hear Bhopal appeal This week is a big one for Union Carbide, the newly elected govern­ ment of India, and the thousands of victims of the 1984 methyl isocyanate disaster at Bhopal. A five-judge panel of the Indian Supreme Court will be meeting to decide essential­ ly whether last year's $470 million Valentine Day settlement should be scrapped and civil and criminal trials resumed. A decision could take weeks. For the past year, the court has been hearing various objections to the settlement by several lawyers representing the victims. It is the continuation of that process that will occupy the court this week. β

March 12, 1990 C&EN

Carbide has said repeatedly that it considers the whole thing over. But it nevertheless was to have filed an affidavit on Feb. 20 with the court outlining why it should not be hearing the petitions. But a Car­ bide spokesman said the company did not file the affidavit and de­ clined to comment further. The case seems destined now to go on for years, because the new successor to Prime Minister Rajiv Gandhi, V. P. Singh, renounced the settlement soon after his election. Last week the government released out of its own funds about $220 million, or about $12 a month each, for distribution over the next three years to 500,000 individuals who lived in the path of the MIC cloud. Carbide meanwhile indicates that

it will not participate in any fur­ ther adjudication in India. It claims moreover that various calculations indicate that only a small percent­ age of the 500,000 claimants were affected in any way. If the Indian court rules in favor of the government and petitioners, Carbide would then be tried in absentia, and India would be forced to appeal to U.S. courts for enforce­ ment. Meanwhile, the $470 million settlement, plus about another $50 million in interest, remains tied up under court order in the State Bank of India until the settlement issue is resolved. The interest alone, Car­ bide says, would be enough to care for the needs of all exposed to the gas. Wil Lepkoivski

Ribozymes cleave AIDS virus genetic material In the experiments, the part of Catalytic ribonucleic acid molecules, or ribozymes, have been designed the HIV genome that contains the to cleave, sequence specifically, the gag gene is such a substrate. The RNA of the human immunodefi­ ribozyme contains the other three ciency virus (HIV). The work could domains of the catalytic site, plus lead to use of ribozymes as thera­ flanking sequences of nucleotides peutic agents against HIV, the virus that are complementary to sequences that causes AIDS, or eventually in at a specific location in the gag gene. anti-HIV gene therapy. The researchers demonstrated that The research was carried out by Nava Sarver, section chief in the the ribozyme cleaves the gag gene developmental therapeutics branch at the intended site in a test tube. of the National Institute of Allergy To evaluate whether such a ribo­ & Infectious Diseases' AIDS branch zyme functions in the complex en­ in Bethesda, Md., working with John vironment of a cell without dis­ J. Rossi, John A. Zaia, and cowork­ r u p t i n g cellular function, they ers at the City of Hope Medical Cen­ engineered a line of human cells ter, Duarte, Calif. [Science, 247, 1222 that are susceptible to infection by HIV so that the cells expressed the (1990)]. The researchers worked with what ribozyme. When exposed to HIV, are known as "hammerhead" ribo­ the transformed cells are able to zymes. The hammerhead structure cleave gag RNA. A particular HIV consists of three stems and a cata­ protein encoded by gag is secreted lytic center made up of 13 conserved by the transformed cells at a much RNA nucleotides arranged in four lower level than by infected con­ domains. The essential constituents trol cells. Sarver says Rossi is experiment­ of the hammerhead can be on sepa­ rate molecules, Sarver says, with one ing with mechanisms for deliver­ RNA strand serving as the catalyst ing the ribozymes as therapeutics. and the other as the substrate. Their most potent application might Ribozyme-catalyzed cleavage occurs be in gene therapy, in which an next to one of the domains of the AIDS patient would receive bone catalytic center, a nucleotide trip­ marrow cells engineered to express let, and it turns out that RNA that the ribozyme. Such gene therapy, contains only the conserved triplet however, is at least several years that marks this cleavage site can away. Rudy Baum serve as a substrate for the ribozyme.