Senesco Technologies' Factor 5A Gene May Regulate Inflammatory Cytokine Proteins.

Business Editors/Health/Medical Writers

NEW BRUNSWICK, N.J.--(BUSINESS WIRE)--July 7, 2003

Senesco Technologies, Inc. ("Senesco" or the "Company") (AMEX:SNT) today announced that preclinical experiments have indicated that the Company's patent-pending Eukaryotic Translation Initiation Factor 5A1 ("Factor 5A") gene may regulate the inflammatory proteins known as cytokines. This discovery may yield a new approach to inflammatory disease research and treatment because inflammatory cytokines have been linked to rheumatoid arthritis, heart disease, Crohn's disease, multiple myeloma and other serious diseases.

Factor 5A appears to control expression of the suite of proteins required for apoptosis (programmed cell death). Such proteins include p53, interleukins, caspases, and tumor necrosis factor (TNF-alpha). Expression of these cell death proteins is required for the execution of apoptosis. The Company has found that blocking Factor 5A by treatment with siRNA or antisense oligoneucleotides inhibits the expression of p53, a major cell death transcription factor that in turn controls the formation of a suite of other cell death proteins. As well, down-regulation of Factor 5A up-regulates Bcl-2, a major suppressor of apoptosis. Blocking Factor 5A also reduces the number of cells undergoing apoptosis.

Dr. John E. Thompson, the Company's Executive Vice President of Research, noted, "Factor 5A is thought to act as a shuttle protein, and may directly or indirectly regulate the expression of all genes required for cell death. These observations indicate that Factor 5A not only controls the formation of proteins required to execute apoptosis leading to cell death, but may also control the formation of inflammatory cytokines -- signals of the immune system that induce inflammation and target cells for apoptosis."

In experiments run on liver cells, TNF-alpha formation induced by interleukin-1 was reduced when the cells were pretreated with antisense oligonucleotides against Factor 5A. Experiments performed on lamina cribrosa cells from human optic nerve heads have shown that apoptosis of these cells can be reduced by 70% when pretreated with a Factor 5A-blocking oligonucleotide before attempting to induce apoptosis with agents known to kill cells. The Company's experiments on human heart tissue have shown a positive correlation of Factor 5A with interleukin-1 and interleukin-18 (IL-1 and IL-18) in ischemic tissue. Ischemia is the restriction of blood and oxygen supply to the heart, which can result in heart attack and heart tissue cell death. The Company is performing ongoing experiments to confirm that heart tissue cell death can be reduced, even after an ischemic event, when the tissue is pretreated to block Factor 5A.

Charles A. Dinarello, M.D., stated, "Inflammatory cytokines are key effectors of the immune system and are the underlying causative agents in most autoimmune disorders and inflammatory diseases. They can serve as the death messages of the immune system, targeting cells that are destined to undergo apoptosis. In our work with human heart tissue, Factor 5A was strongly correlated (R=0.8) with mRNA levels of the pro-inflammatory cytokines IL-1 and IL-18. Of interest is that this correlation exists in heart muscle taken from patients with ischemic disease. Our experiments will determine if inhibiting Factor 5A prior to induced ischemia, can protect heart cells from apoptosis. Additionally, current therapies for inflammatory diseases such as arthritis and Crohn's disease focus on blocking single cytokines or other single elements of inflammation. The ability of Factor 5A to inhibit cytokine components of the inflammatory cascade could be a significantly novel target for treating many diseases."

About Senesco Technologies, Inc.

Senesco takes its name from the scientific term for the aging of plant cells: senescence. The Company has developed technology that regulates the onset of cell death. Delaying cell breakdown in plants extends freshness after harvesting, while increasing crop yields, plant size and resistance to environmental stress for flowers, fruits and vegetables. The Company believes that its technology can be used to develop superior strains of crops without any modification other than delaying natural plant senescence. Senesco has begun to explore ways to trigger or delay cell death in mammals (apoptosis) to determine if the technology is applicable in human medicine. Accelerating apoptosis may have applications to development of cancer treatments. Delaying apoptosis may have applications to certain diseases such as Alzheimer's, glaucoma, ischemia and arthritis, among others. Senesco partners with leading-edge companies and earns research and development fees for applying its gene-regulating platform technology to enhance its partners' products. Senesco is headquartered in New Brunswick, New Jersey, and utilizes research laboratories at the University of Waterloo in Ontario, Canada, and the University of Colorado in Denver, Colorado.

An archive of the Company's press releases is available at www.senesco.com.

Certain statements included in this press release are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results could differ materially from such statements expressed or implied herein as a result of a variety of factors, including, but not limited to: the development of the Company's gene technology; the approval of the Company's patent applications; the successful implementation of the Company's research and development programs and joint ventures; the success of the Company's license agreements; the successful conversion of the Company's letter of intent into a license agreement; the acceptance by the market of the Company's products; competition and the timing of projects and trends in future operating performance, as well as other factors expressed from time to time in the Company's periodic filings with the Securities and Exchange Commission (the "SEC"). As a result, this press release should be read in conjunction with the Company's periodic filings with the SEC. The forward-looking statements contained herein are made only as of the date of this press release, and the Company undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstances.