Isis Pharmaceuticals Inc. announced Wednesday that it hasbeen awarded a two-year, $500,000 small business innovativeresearch (SBIR) grant by the National Institute of Allergy andInfectious Diseases (NIAID) to conduct research on antisensecompounds that target a particular structure on messengerRNA.

Jacqueline Siegel, Isis' vice president and chief financial officer,told BioWorld that the company will study the inactivation ofspecific messenger RNA through antisense-directed action uponthe 5' cap, a chemical structure at one end of most cellular andviral messenger RNAs. The approach, Siegel said, offers thepotential for a highly controlled method of blocking the actionof messenger RNA rather than relying on cellular mechanism todestroy RNA.

Isis (NASDAQ:ISIP) of Carlsbad, Calif., said that the 5' cap playsa pivotal role in the maturation, transport, stability andinitiation of protein synthesis in messenger RNA. The companyhopes the technology may be useful in the development oftherapeutics for infectious and host diseases.

Isis was awarded $1 million in SBIR grants from NIAID lastAugust to characterize antisense oligonucleotides againstreplication of a human papillomavirus (which causes genitalwarts) and against herpes simplex virus. Government fundingfor the company's work in this area began in 1991, when Isiswas awarded a $50,000 SBIR grant to study the chirality ofmodified oligonucleotides.

The company's lead oligonucleotide-based drug candidate, ISIS2105, is in Phase II development for the treatment of genitalwarts. A second agent, ISIS 2922, is in Phase I development forthe treatment of retinitis in AIDS patients.

-- Karl A. Thiel Associate Editor

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