Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
PR Newswire, Monday, 2 December 1996.
The article, entitled, "Altered mRNA Splicing and Inhibition of Human E- selectin Expression by an Antisense Oligonucleotide in Human Umbilical Vein Endothelial Cells," was authored by Thomas P. Condon, M.S., and C. Frank Bennett, Ph.D., of Isis Pharmaceuticals.
E-selectin, a member of the cell adhesion family of molecules, plays a major role in the recruitment of white blood cells or leukocytes to areas of infection or disease. E-selectin has been shown to be transiently expressed in acute inflammatory reactions such as reperfusion injury, sepsis, allergic and other disorders and thus, inhibition of E-selectin expression may be of potential benefit in inflammatory diseases. In this study, an antisense compound, ISIS 4730, designed to bind to human E-selectin mRNA, was shown to reduce mRNA and protein expression levels in human umbilical vein endothelial cells (HUVEC). It was also shown that reduction of the target mRNA was accompanied by the appearance of a novel transcript containing RNA sequences which are normally removed as the mRNA matures and prior to translation into a protein. The retention of this novel transcript demonstrated that the antisense compound was inhibiting splicing, the process by which the intervening sequences are normally removed from the mRNA. This study thus indicates that antisense can be used in a variety of ways to modulate early steps in RNA metabolism, permitting a broader use of antisense to inhibit protein production.
"This article is another important milestone in providing strong evidence of the antisense mechanism of action as well as in demonstrating that antisense compounds work in a variety of ways to inhibit protein production," said Stanley Crooke, M.D., Ph.D., Chairman and Chief Executive Officer. "The more we explore and understand the full breadth of utility of antisense technology, the better we will be able to design and develop antisense drugs with greater potency, safety and effectiveness."
This press release contains forward-looking statements concerning the value and utility of antisense technology. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics. Actual results could differ materially from those projected in this release. As a result, the reader is cautioned not to rely on these forward-looking statements.
These and other risks are described in additional detail in Isis' Annual Report on Form 10-K for the year ended December 31, 1995 and in the Company's most recent quarterly report on Form 10-Q filed with the Securities and Exchange Commission, copies of which are available from the company.
Isis Pharmaceuticals, based in northern San Diego County, is engaged in the discovery and development of novel human therapeutic compounds. Isis has four compounds in human clinical trials: ISIS 2922, to treat CMV-induced retinitis in AIDS patients, is in Phase III clinical trials; ISIS 2302, an inhibitor of ICAM-1, is in Phase II clinical trials for renal transplant rejection, rheumatoid arthritis, psoriasis, Crohn's disease and ulcerative colitis; and ISIS 3521/CGP64128A and ISIS 5132/CGP69846A, both anticancer compounds, are in Phase I clinical trials. The company also has several additional compounds in preclinical development. Isis' broad medicinal chemistry and biology research programs support efforts in both antisense and combinatorial drug discovery.
CONTACT: Jane Green, Senior Director, Investor Relations, 619-603-3880, or http://www.isip.com/ 06:00 EST
961202
PR961201
Copyright © 1996 - PRNewswire. All rights reserved. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through PRNewswire, Permissions, 810 Seventh Ave., 32nd Floor, New York, NY 10019 http://www.prnewswire.com.
AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Elton John AIDS Foundation UK, the National Library of Medicine, AIDS Walk of Orange County, and donations from users like you.
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Copyright ©1980, 1996. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .