From Generalized to Precise

Genetics intrigues me because of its ability to explain the mysteries of biology. It helps us understand the biological programming behind all life forms, including ourselves. In the past 100 years we have discovered DNA, developed ways to read it, and now we are working on methods to write and edit this code. It is the growing understanding of the universal language of life that provides us the incredible power to shape the future of humanity. This is a scientific revolution that, with the right amount of careful consideration, will change the human condition for the best. Most obviously it will transform healthcare. 

A person’s healthcare treatment today is based on what works for the average human in a population of 7 billion. But with the decreasing cost of genome sequencing and a better understanding of the genome itself, a person’s treatment is becoming increasingly based on their biology. Healthcare is therefore beginning to shift from generalized to precise. 

One of these novel precise treatments is gene therapy and the researchers at Asokan Lab work to find novel ways of improving it. Gene therapy is a technique that targets the cause of the disease by finding genetic solutions for genetic disorders. The classic model of gene therapy is to use a viral vector to deliver a working copy of a defunct gene. The introduction or change of genetic material into the cells of a patient is all about changing how a protein or group of proteins is produced by the cell. For example, one of the genetic disorders targeted by the project I’m currently working on is Duchenne muscular dystrophy (DMD). Patients with DMD have severely reduced muscle strength as a result of alteration to a protein called dystrophin that helps keep muscle cells intact. The goal of the project I’m working on is to increase levels of functional dystrophin expression in DMD patients through RNA editing. 

The central dogma of biology is that the pattern of information flow in our cells goes like this: From DNA to new DNA (DNA replication), from DNA to new RNA (transcription), from RNA to new proteins (translation). RNA gene therapy targets disease-causing mutations at the translation step. In our project, we aim to edit RNA via trans-splicing by manipulating the splicing pathway by which pre-mRNA turns into mRNA. In doing so, we can replace a mutant exon in the DMD mRNA transcript, which is known to abolish dystrophin production, with a functional version of that exon. When this correction is made, therapeutic levels of dystrophin restoration can occur. DMD is only one of the multiple genetic disorders we will be targeting with this RNA editing mechanism. I’m very excited to be working on a project with this level of therapeutic novelty and medical relevance.

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