2nd Place


Sophia Spiegel

Bergen County Academies 
Teacher: Judith Pinto


The Gift of Sight: Gene Therapy for Leber’s Congenital Amaurosis

A life-altering condition, Leber’s Congenital Amaurosis takes from those it affects what is arguably the most important sense, sight. At its core, it is a progressive retinal degenerative disease, characterized by severe infantile-onset rod-cone dystrophies resulting from mutations in the genes responsible for the development of normal vision. …The early age at which the symptoms of this disorder begin to present themselves has made this a focus for researchers seeking potential methods of treatment for genetic conditions. With new knowledge regarding the genes that cause this disorder, treatment of it through novel methods of targeted gene therapy appears attainable… 

…The protein associated with RPE65, retinal pigment epithelium-specific 65-kD, is essential for the visual cycle, the process through which light is absorbed and converted into electrical signals transmitted to the brain. The RPE65 protein is specifically responsible for converting a molecule known as all-trans retinal, a product of the visual cycle, into 11-cis retinal, that allows for the cycle to begin anew…

…several trials have attempted to use recombinant adeno-associated virus 2/2 (rAAV2/2) vectors carrying RPE65 complementary DNA to preserve or improve photoreceptor function and thus vision. rAAV2/2 based genomic engineering uses the adeno-associated virus (AAV) to deliver specific single-strand gene sequences to cells. …Thus the goal of current research is to replace the mutated RPE65 sequences with the correct RPE65 complementary DNA using AAV as a delivery mechanism (6)…

…Two subjects groups were treated with either a high dose of a rAAV2/2 vector carrying the RPE65 cDNA or a lower dose of the vector and then monitored over a three-year period. Temporary improvements in retinal sensitivity were seen, albeit to varying extents, in half of the subjects...Thus it is possible that the human need for RPE65 was not met to the extent necessary for noticeable improvements in vision (1)…

…solving this issue have been made since, namely through modifications of a more effective AAV2/5 vector. A 2016 trial using mice and the modified AAV2/5 vector, worked to optimize transduction, transcription, and translation through modifications of the hRPE65 promoter and adjustment of the DNA sequence carried by the virus. The goal was to modify the vector to deliver a greater amount of RPE65 protein while not exceeding the maximum tolerated vector dose (4). Results were extremely positive and mice saw a 300-fold improvement in retinal function suggesting great potential for this method in human trials…

…Gene therapy, using viral vectors or otherwise, is opening doors for effective treatment of disorders that were once accepted as lifelong and untreatable. If research continues at this pace, conditions due to genetic mutations and errors may one day become as treatable as a cold.