M KELLY N 722.

01 Immunology April 1, 2009

Dr. Lambton

How RNA inference could be used to target macular degeneration.

This executive summary will conceptualize how macular degeneration can be

suppressed or turned off with the emerging biotechnology of RNA inference
(RNAi). The basis for this summary is from the April 2007 issue of International
Immunology; Can interfering with RNA shut down the macular degeneration
process? (Kong, Ruan, Cui, Wang & Le, 2006). The article describes the
emerging field (market) of gene silencing of specific mechanisms of the immune
system one of which RNAi targets endothelial blood vessel and affects cell
surface receptors are believed to be involved in progression of macular
degeneration. Neovascular or commonly known as “wet” age-related macular
degeneration (AMD) is specific to the endothelia cells of the macular
vasculature. The complete etiology of AMD is not fully known, however, several
concepts of the process have been established. There is a genetic influence on
vascular endothelial growth factor (VEGF), which as the body ages past 50, can
develop into an abnormal reparative response perhaps due to the lower levels of
oxygen in the vasculature as the body ages and in which basal deposits play a
role. The once appropriate genetic mechanism that controlled the growth of
endothelial cells in the retinal vessels becomes inappropriate and now causes or
deregulates and allows uncontrolled cellular growth which in turn causes
hemorrhage and fluid leakage in the sub tissue of the retina and subsequent
vision loss. The gene called transforming growth factor-beta (TGF-b) in fact
appears to trigger an initiation of cell injury. Laser therapy has been the primary
treatment but only prevents further vision loss at it’s best. The devastation of
limited vision is a reality to an aging yet mobile and cognitively intact
population; a cure is needed and perceived as highly marketable.

RNAi is a dynamic and evolving field of research in which the age-related

progression of AMD, a disease with a definitive genetic pathway that could be
“switched off” with gene therapy. The gene silencing properties of RNAi in AMD
has been associated with that inhibition or regulation of TGF-b. RNAi influences
the existing RNA is into altering its translation of genetic coding of the DNA,
which in the case of AMD, is the VEGF’s TGF-b. Targeting AMD by injecting RNAi
into the vitreous cavity is one proposed method of gene silencing, yet the
unknowns of RNAi treatment in AMD are vast.

Researchers have yet to identify if this delivery of RNAi actually works safely and
Kong, Y, Ruan, L., Cui, Y, Wang, J and Le, Y. (2006) “Rna interference as a novel and powerful
tool in immunopharmocological research” International Immunophramacology 7,(4).
M KELLY N 722.01 Immunology April 1, 2009
Dr. Lambton

effectively. Will the RNAi target only the TGF-b in the eye and not other areas of
the body? Also, how long will the genetic silencing last and what the risk-benefit
ratio looks like? Time will hopefully tell as clinical studies of RNAI and AMD are
currently being carried out.

Kong, Y, Ruan, L., Cui, Y, Wang, J and Le, Y. (2006) “Rna interference as a novel and powerful
tool in immunopharmocological research” International Immunophramacology 7,(4).