Gene Therapy in Action: Adeno-Associated Viral Vectors

03/09/22 • 11 min

Adeno-associated viral vectors, or AAVs, are the tiny shells of viruses. And today they are the most common vessels for delivering gene-based therapies. In this episode, we’ll launch into the past, present, and future of AAVs.

Imagine a rocket ship blasting off from Earth with cargo bound for a distant space station, and you have a pretty good idea what adeno-associated viral vectors are all about. But instead of ferrying hardware and supplies, AAVs carry genes.

It’s an achievement nearly six decades in the making. That might seem like a long time to tinker with something smaller than the tiniest single-celled organism. But just like building a rocket ship destined for the deep reaches of space, the development of AAV vectors required patience, persistence, and a few leaps of faith.

In the era before DNA sequencing and gene cloning, scientists in the 1960s realized that adeno-associated viral vectors could be a window into understanding genetic variations in viruses – and eventually other organisms, too.

The fact that AAVs were immunologically distinct from other viruses made them curious things.

So in the 1970s, AAV research took off in three directions. One determined that the simple AAV DNA could be rewritten and edited in a lab. The second found that although these small viruses can infect humans, they don’t replicate without a “helper virus” (such as adenovirus). In the absence of another virus, they remain latent, and appear to be of little threat to human health. The third investigated whether AAVs could become vectors for transferring genes from one organism to another.

This all culminated in 1978, when the first cloned AAV was generated and was successfully transferred to a cell of the E. coli bacterium, where it produced 50 new colonies of AAVs.

So now we had proof that adeno-associated viruses could be artificially produced, that they

could be hollowed out and filled with other genetic material, and that they could potentially be

a vector for delivering genes without harming their new host.

By the 1980s, we had the capability to build lots of viral rocket ships and fill them with genetic cargo, we just needed a destination to send them. Enter the burgeoning field of gene therapy, with its focus on developing treatments for genetic diseases like cystic fibrosis, hemophilia B, Parkinson’s, and more.

Research has continued and today, adeno-associated viral vectors are a mainstay of gene therapy development. While progress is necessarily slow, gene therapy is a science that is aiming for the stars. And with AAV vectors, they are now within our reach.

For more education on gene therapy, visit www.genetherapynetwork.com.

The fact that AAVs were immunologically distinct from other viruses made them curious things.

This all culminated in 1978, when the first cloned AAV was generated and was successfully transferred to a cell of the E. coli bacterium, where it produced 50 new colonies of AAVs.

So now we had proof that adeno-associated viruses could be artificially produced, that they

could be hollowed out and filled with other genetic material, and that they could potentially be

a vector for delivering genes without harming their new host.

For more education on gene therapy, visit www.genetherapynetwork.com.

Previous Episode

The Future of Gene Therapy and Genetic Diseases

Peek into the future of gene therapy and its capacity to treat – maybe eliminate – genetic diseases like cancers and hemophilia. Plus, the potential to reverse the effects of aging.

It’s a future scientists have been working toward for years: How to treat complex health problems with gene therapy. And researchers have been making progress. Diagnoses once thought to be fatal are now being looked at in a new light.

This is a welcome sight for physicians, caregivers, and – most of all – for the patients living with these genetic diseases.

One disease that’s impacting lives worldwide is cancer. Nearly 40% of the world’s population will be diagnosed with it at some stage of life.

Typically, cancer treatment takes three forms: chemotherapy, surgery, or radiation therapy. Targeted drug therapies also exist, which work by identifying and attacking cancer cells individually.

But the treatment that many believe has the most potential is immunotherapy.

Immunotherapy uses a patient’s immune system to target and destroy cancerous tumors. And a specific type of immunotherapy known as Chimeric antigen receptor (or CAR) T-cell therapy has particular promise.

Over the last few years, progress with this new class of gene-based treatment has accelerated.

CAR T-cell Therapy is when a patient's own immune cells – the white blood cells called T cells – are genetically altered to target and attack a specific cancer within the body. These cells are first removed from the patient’s blood. Their genes are then altered to produce proteins called CARs, which allow the T cell to better recognize – and attack – specific cancer cells. When the altered immune cells are reintroduced into the patient's bloodstream, these proteins latch onto both healthy and cancerous cells, destroying the cancerous cells while leaving the healthy cells unharmed.

CAR T-cell Therapy has the ability to revolutionize cancer treatment and prevent relapse, as these cells can potentially continue to attack cancerous cells in a patient’s body for years. But it’s not a solution for everyone. Only about 40% of patients have long-term responses.

But if this therapy achieves what scientists believe it can, chemotherapy could be a thing of the past, and when it comes to the future of gene therapy and genetic diseases, there's reason for optimism.

For more education on gene therapy, visit www.genetherapynetwork.com.

Next Episode

ALS, DMD and Adapting Treatment Mechanisms for Genetic Variations

In this episode, we’ll dig into the different mechanisms by which gene therapy can potentially treat specific genetic diseases – such as amyotrophic lateral sclerosis, or ALS, and others.

In 1993, a multinational group of scientists and doctors solved a medical mystery 150 years in the making.

And they did it, in part, by examining the genealogy of a particular family in Vermont. In 1835, a farmer named Erastus Farr died of a mysterious illness characterized by a progressive weakening of his muscles followed by paralysis and respiratory failure.

Thirty years later, his descendent Samuel Farr died of the same condition, as did four of Samuel’s eight children, the youngest at the age of 27.

By 1880, the Canadian physician Sir William Osler had studied the Farr family phenomenon and concluded that they all suffered from a newly identified disease known as amyotrophic lateral sclerosis.

But how could this frightening condition be passed from one generation to the next?

Over the next hundred years, scientific interest in the disease grew, especially after the legendary baseball player Lou Gehrig died of the disease in 1941.

But there was still a mystery: while 90% of ALS cases are considered sporadic – meaning there is no hereditary connection – the other 10% of cases seemed to run in families, like the Farrs.

After the dawn of the genetic age, scientists began to suspect a gene variation was at the heart of the mystery. And then finally, in 1993, scientists including Robert Brown at the University of Massachusetts medical school, who studied the Farr family and others while also investigating the human genome, uncovered the answer.

In some ALS patients, a variant of a single gene, called SOD1, can cause a buildup of toxic proteins in the brain, leading to the various symptoms that characterize the disease. In this case, the goal of gene therapy is to block or silence the abnormal production of a protein.

And solving that mystery has paved the way for gene therapy, perhaps someday soon, to provide the first known treatment for familial ALS.

For more education on gene therapy, visit www.genetherapynetwork.com.