Point: Treating Human Genetic Disease One Base Pair at a Time: The Benefits of Gene Editing

摘要

The observation that the human genome can be mapped represented a major inflection point in biology. The decision to sequence the human genome was met with excitement and trepidation. The arguments for and against sequencing included whether the technology was sufficiently advanced, whether it would divert resources from elsewhere, and whether it could have unknown negative societal benefits. Some 2 decades later, the delivery of the first draft of the human genome was received as a crowning achievement of science. Now, high-throughput genomic technologies have potentiated mutation discovery across many disorders and have carried with them the promise that treatments for these ailments will eventually follow. Indeed, terminology such as a??individualized medicine,a?? a??precision medicine,a?? a??personalized medicine,a?? and other similar terms abound, and these imply that by reading the genome; integrating worldwide data sets with clinical observation; and real-time biometric readings, diagnosis will be expedited and treatments will be tailored to the needs of each individual genome. Reflecting on the genome journey, there is no question that giant advances in diagnostics and therapy have been made. We celebrated gene therapy trials such as Ashanti DeSilva's to treat adenosine deaminase deficiency in 1990 (1) and some forms of retinal degeneration (2). We cheered when enzyme replacement therapy and allogeneic stem cell transplants showed some effectiveness in catastrophic inborn errors of metabolism (3) such as Pompe disease, and, as RNA therapeutics emerged, we marveled at the early successes of antisense oligonucleotides delivered intrathecally to treat spinal muscular atrophy (4), to name but a few exemplars. Unfortunately, these successes represent a handful of a??solutionsa?? in the backdrop of 10000+ rare and ultrarare genetic diseases (https://rarediseases.org/). Under current paradigms it is difficult to see a path to more a?|