How to Add Something to Your Genome

By Max Yang '25

Many human diseases are caused by defected genes and thus, protein malfunctioning. And most of them remain as an unsolved mystery in modern medical science, still torturing those who accidentally have such mutated genes. Are there any ways to fix those genetic errors and restore people to health? Luckily, adeno-associated virus’ function in gene transferring shows a promising prospect in this field.

One thing to note is that adeno-associated virus (AAV) is only a vector, or a “vehicle” in the process of gene therapy. Since genes edited by technologies like CRISPR do not function if they are directly introduced to a cell, a carrier called a vector is genetically engineered to deliver the gene, and AAV is one of them.

The primary reason why AAV has attracted considerable interest from gene therapy scientists is its low pathogenicity. Also, it infects not only dividing cells, but also non-diving cells, making it a better option than another candidate of effective gene therapy—retrovirus. Development of AAV as a gene therapy vector requires the replacement of a segment of its genome with therapeutic genes. By injection to target tissue, edited AAV enters a cell’s nucleus just like a normal virus and releases its genetic materials in it. Since the gene replacement disables them from replicating, these genetic materials remain in the nucleus as an extrachromosomal episome—not integrated into the cell’s genome, which eliminates the possibility of passing them on to future generations of cells. The episome is transcribed and translated alongside with the host cell genes. In this way, unless the cell divides and dilutes the non-replicating AAV genome, expression of the therapeutic genes transferred by AAV persists for the life of the host cell, which ensures a stable and long-term curative affect. Perhaps the only disadvantage of AAV as an approach of gene therapy is its low capacity—it can only accommodate 4.8 kilobase genes, which means that larger genes are not suitable for an AAV vector.

Multiple clinical trials have been carried out worldwide to test AAV’s effectiveness in curing a number of gene-related diseases, including Parkinson’s disease, hemophilia, congestive heart failure, spinal muscular atrophy, etc., which obtained promising results. Maybe in the future, AAV will revolutionize the field of gene therapy with its huge potential, basically by adding something to your genome.

Sources:

https://www.youtube.com/watch?v=CMFUbSfUEYk

https://medlineplus.gov/genetics/understanding/therapy/procedures/

https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(11)70039-4/fulltext