Key Takeaways
- Genes provide instructions for building and expressing proteins which execute bodily functions and express inherited traits.
- Changes or mutations in certain genes can disrupt protein production and function and cause genetic conditions.
- Gene therapy uses modified genetic material to treat or prevent genetic disease.
- Vectors, often modified viruses, are used to deliver new genetic instructions inside of cells.
A familiar “ding” and “buzz” from my phone signals the newest, juiciest, headlines awaiting my careful scroll during my morning news binge. It's December 8th, 2023 - a big day in the scientific community that has been waiting for FDA approval of the first gene editing therapy. It’s an even bigger day in the lives of over one hundred thousand Americans who have sickle cell disease. This milestone marks the beginning of a new era of precision medicine and possible therapeutics for genetic conditions.
But what exactly is gene therapy? And how does it work? (I thought CRISPR was a setting on my air fryer.) What does it take to develop a treatment for rare conditions, and what are the potential expansions of this technology? If you have these questions, join me as I unravel the fascinating frontier of gene therapy, explore the promises and pitfalls, and discover remarkable examples of its life-changing potential.
Genetic Blueprint Basics
Our genetic information resides within 23 pairs of chromosomes found in every cell of our bodies. These chromosomes contain DNA, the genetic code that dictates our traits and characteristics. Within the DNA, specific segments called genes act as the blueprints for building the proteins that execute our bodily functions and express our inherited traits, such as eye color and hair texture.
Genetic changes, known as mutations or variants, are a natural part of our genetic instructions. These alterations can arise from various sources, including environmental factors and inheritance from our parents. While some mutations have no discernible impact, others can lead to disease by disrupting protein production or function. Genetic conditions can manifest through different inheritance patterns, from single mutations to complex combinations.
Gene Therapy: A New Frontier
Treatments for inherited diseases have traditionally focused on managing symptoms rather than addressing the underlying genetic causes. However, gene therapy offers a promising alternative by correcting disease-causing mutations and their effects on protein production. With less than 5% of rare genetic diseases having FDA-approved treatments, the opportunity to expand therapeutic options for genetic diseases is enormous. Gene therapy aims to fill this gap by providing focused treatments to improve or even cure genetic conditions, with the goal of enhancing the quality of life for many affected individuals.
Gene Therapy in Action
What is gene therapy? Simply put, it involves using genetic material to treat or prevent disease. Gene therapy involves delivering a new set of genetic instructions stored in DNA or RNA to cells through a viral vector (more on this below). Gene therapy uses different mechanisms to appropriately target and treat different types of genetic mutations. These mechanisms can include:
- Gene Addition: Delivering a new working copy of a gene to cells to create the correct amount of protein.
- Gene Silencing: Inactivating a gene to prevent or suppress abnormal protein production.
- Gene Editing: Changing or deleting a part of a gene that is already present in the cells to correct protein production.
There are two general approaches to administering gene therapy:
- Direct, in-vivo: Genetic material is delivered directly into your cells, typically through injections or infusions. One example of in-vivo gene therapy is Onasemnogene abeparvovec, a gene therapy designed to treat spinal muscular atrophy.
- In-direct, ex-vivo: Cells are first removed from the body, treated with gene therapy, and then returned to the individual. This is the mechanism of the CRISPR-based therapy that the FDA approved in December 2023 for sickle cell disease.
Vectors: Uber-cool genetic chauffeurs
What are vectors? Vectors are typically viruses that have been modified by removing their viral genes, leaving an empty shell that is effective at entering cells in the body. Once inside a cell, vectors deliver the new genetic instructions, which are incorporated and expressed by the cell.
Consider vectors like genetic chauffeurs that transport new genetic material to its final destination – your cells. Like requesting a ride on a rideshare app, you can decide which vehicle and driver best suit your needs. The size, comfort level, and amount of baggage you are transporting may determine if you choose an economy or XL ride. Do you need to add a stop during your trip (ex-vivo) or proceed directly to your destination (in-vivo) - let your driver know. While more complicated than a five-star driver rating system, scientists also use safety and past performance to select the best vector, or vehicle, to deliver the specific genetic instructions. Who knew viruses could deliver more than a common cold or unruly GI bug? This is the type of “going viral" I can root for.
Perhaps you aren’t sold on the idea of letting viral shells loose in the body or have questions about the safety of these therapies. Stay tuned for the next installment in our exploration of gene therapy, in which we will dive deeper into how these technologies work and what it takes to bring them to market. Together, we'll unravel the mysteries, confront the challenges, and celebrate the triumphs of gene therapy.
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