Dawn of ocular gene therapy: implications for molecular diagnosis in retinal disease.

TitleDawn of ocular gene therapy: implications for molecular diagnosis in retinal disease.
Publication TypeJournal Article
Year of Publication2013
AuthorsZaneveld, J, Wang, F, Wang, X, Chen, R
JournalSci China Life Sci
Date Published2013 Feb
KeywordsAnimals, DNA Mutational Analysis, Genetic Therapy, Genetic Vectors, High-Throughput Nucleotide Sequencing, Humans, Leber Congenital Amaurosis, Macular Degeneration, Molecular Diagnostic Techniques, Precision Medicine, Retinal Diseases, Retinitis Pigmentosa

Personalized medicine aims to utilize genomic information about patients to tailor treatment. Gene replacement therapy for rare genetic disorders is perhaps the most extreme form of personalized medicine, in that the patients' genome wholly determines their treatment regimen. Gene therapy for retinal disorders is poised to become a clinical reality. The eye is an optimal site for gene therapy due to the relative ease of precise vector delivery, immune system isolation, and availability for monitoring of any potential damage or side effects. Due to these advantages, clinical trials for gene therapy of retinal diseases are currently underway. A necessary precursor to such gene therapies is accurate molecular diagnosis of the mutation(s) underlying disease. In this review, we discuss the application of Next Generation Sequencing (NGS) to obtain such a diagnosis and identify disease causing genes, using retinal disorders as a case study. After reviewing ocular gene therapy, we discuss the application of NGS to the identification of novel Mendelian disease genes. We then compare current, array based mutation detection methods against next NGS-based methods in three retinal diseases: Leber's Congenital Amaurosis, Retinitis Pigmentosa, and Stargardt's disease. We conclude that next-generation sequencing based diagnosis offers several advantages over array based methods, including a higher rate of successful diagnosis and the ability to more deeply and efficiently assay a broad spectrum of mutations. However, the relative difficulty of interpreting sequence results and the development of standardized, reliable bioinformatic tools remain outstanding concerns. In this review, recent advances NGS based molecular diagnoses are discussed, as well as their implications for the development of personalized medicine.

Alternate JournalSci China Life Sci
PubMed ID23393028
PubMed Central IDPMC3567286
Grant ListR01EY018571 / EY / NEI NIH HHS / United States
R01 EY022356 / EY / NEI NIH HHS / United States
R01 EY018571 / EY / NEI NIH HHS / United States
T32 GM008307 / GM / NIGMS NIH HHS / United States
R01EY022356 / EY / NEI NIH HHS / United States
T32 EY007102 / EY / NEI NIH HHS / United States

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