===========================
                        JeffNEWS, February 21, 1995
                        ===========================


How `Antisense' Gene Therapy for Restenosis Works
-------------------------------------------------

The research carried out by Andrew Zalewski, MD, research director, 
division of cardiology, and Yi Shi, MD, PhD, assistant research director, 
cardiology, to treat restenosis is part of the new biotechnology called 
"antisense." 

Antisense technology tries to halt disease by stopping, or temporarily 
suspending, the activating energy of genes that cause the disease. In this 
case, Drs. Zalewski and Shi identifed one gene stimulating the growth of 
scar tissue on the inner walls of arteries recently cleared by balloon 
angioplasty.

The gene which Drs. Zalewski and Shi identified early in their research 
as stimulating restenosis is known as the "c-myc" gene. They found that the 
effect on artery walls of balloon angioplasty activates the c-myc gene, 
which in turn stimulates growth of smooth muscle cells. This produces scar 
tissue on the arteries' inner walls, narrowing the arteries and blocking or 
slowing the blood flow through them.

Their key finding was to discover that the action of the c-myc gene 
could be "blocked" by using pieces of synthetic DNA called antisense 
"oligomers." This blocking inhibits cell growth and secretion of collagen, 
major components of the scar tissue. When the oligomers are delivered into 
the vessel wall, the growth of soft-muscle scar tissue halts. In this 
particular research, the oligomers are the "antisense" agents. 

The blocking is achieved by administering the antisense oligomers to the 
c-myc gene's so-called "messenger RNA." When that occurs genetically, the 
binding effect is analogous to putting a padlock on the c-myc gene, so that 
it can't activate the smooth-muscle cells in artery walls to build up and 
slow blood flow. 


------------------------------------------------------------------------------
Information provided by:  Editor, JeffNEWS
                          (215) 955-6204
------------------------------------------------------------------------------