Ohio University researchers for the first time have usedantisense technology to protect animals from infection by aleukemia-causing retrovirus.
The study supports efforts to develop antisense-basedtreatments for retroviruses that cause leukemia and AIDS.
The scientists describe in today's Proceedings of the NationalAcademy of Sciences the construction of transgenic mice thatcontain an antisense gene that is complementary to a viral RNAsequence.
The gene encodes antisense RNA, which binds to itscomplementary sequences on genomic viral RNA. This RNA-RNA binding prevents viral proteins from binding to the RNA,thereby disrupting virus formation.
When antisense gene-containing transgenic mice in the studywere exposed to Moloney murine leukemia virus, nonedeveloped leukemia.
"This is one of the first dramatic demonstrations of the use ofantisense technology in whole animals," said Dr. JamesHawkins, president of Synthecell Corp. and editor in chief of thejournal Antisense Research and Development. The resultsreinforce the potential applications of antisense in treatinggenetic diseases, he said.
Most antisense strategies block the expression of a targetedgene or RNA into a protein. This usually leads to a reducedamount of the protein, but rarely to total suppression of viralinfection, said study director Dr. Thomas Wagner.
The Ohio team's technique takes a different tack thatcompletely blocks viral infectivity. The antisense RNAexpressed by the transgenic mice blocked packaging -- theattachment of viral proteins to viral genomic RNA -- which is aprerequisite to virus assembly.
The study demonstrates that there are more applications forantisense than just blocking gene expression, said GileadSciences Inc. President Michael Riordan. Packaging is just oneexample of events that can be disrupted using nucleic acids, hesaid.
"Once people know that ... getting antisense RNA into theappropriate cells will have a biological effect, they are muchmore motivated to develop delivery techniques that will beclinically useful," said Dr. W. French Anderson, chief ofmolecular hematology at the National Heart, Lung, and BloodInstitute.
Biotechnology companies developing antisense-basedpharmaceuticals include Synthecell, Gilead, Genta Inc. and IsisPharmaceuticals Inc.
Wagner next plans to infect mice with the same virus and treatthe animals either with stabilized antisense oligonucleotides orby a gene therapy vector approach that delivers the antisensegene to white blood cells. Such studies show how diversetechniques, namely synthetic drugs and gene therapy, can beused to target disease, said Hawkins.
-- Carol Talkington Verser, Ph.D. Special to BioWorld
(c) 1997 American Health Consultants. All rights reserved.