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Honorable Mention Excerpts

Lucy Liu

Illinois Mathematics and Science Academy 
Aurora, IL
Teacher: Crystal Randall

 

Gene Therapy for RPE65-associated Leber’s Congenital Amaurosis

We are constantly using sight to interpret our surroundings and navigate the world around us. Clear vision is one of mankind’s most useful tools, but it’s often unavailable to individuals suffering from vision disorders such as Leber’s Congenital Amaurosis (LCA). Thankfully, modern medicine offers a potential treatment for some LCA patients. By replacing a mutated gene with a working one, gene therapy can be used to reactivate the visual cycle and drastically improve vision for RPE65-associated LCA…

…For individuals carrying the RPE65 gene mutation, RPE65 enzymes don’t work properly, and insufficient amounts of 11-cis-retinol are produced for the visual cycle to run and photoreceptor cells to function. Even though the photoreceptor cells stop working, causing vision to fail, they are still present and healthy in the retina (Manning, 2008). It’s like having an old palette of watercolor paints: when the palette is dry, the paint doesn’t work, but once water is added, the palette will be usable again…

…For cells to use a new gene, the new genetic information must first be transferred into the photoreceptor cells through a vector. Conveniently, naturally occurring tools which can inject new DNA into cells already exist in the form of viruses. Viruses reproduce by incorporating their own genetic information into host cells, which are then hijacked to clone copies of the invading virus. Through careful genetic engineering, scientists are able to create viral vectors for therapeutic genes by replacing the DNA section encoding the infectious viral genome with the desired gene instead (Kay, Glorioso, & Naldini, 2001). These viral vectors are then able to deliver DNA to diseased cells…

…There are numerous types of viral vectors to select from, but most RPE65-associated LCA studies use an adeno-associated virus (AAV) as a vector. This is because the non-pathogenic adeno-associated viruses do not cause immune responses and are the appropriate size for carrying the RPE65 gene. AAV vectors are also appealing because they allow prolonged expression of the delivered gene (Daya & Berns, 2008).

…Gene therapy trials for RPE65-associated LCA have shown promising results so far…They further found that patients experienced significant improvements in light sensitivity and visual acuity, which lasted for at least 1.5 years, and hypothesize that the two studies had different results because the patients had different levels of initial visual capability…