How AAVs are Transforming Gene Therapies
AAV gene therapy is a leading biopharma innovation, offering safe, non-pathogenic viral delivery. Discover how these advanced therapies work and the innovative companies driving their development.
Table of Contents
What is Gene Therapy?
Before understanding the intricacies of AAV gene therapies, it is important to understand the category of gene therapies as a whole. Gene therapies, as discussed in our article “What is Cell & Gene Therapy?”, are treatments that involve the process of altering, removing, replacing, or adding a gene.
The genes that are targeted are those that are causing a disease or disorder in an individual. It offers an alternative solution to simply managing symptoms, as gene therapies aim to target the issue on a fundamental level.
Viral vs. Non-Viral Systems
When discussing gene therapy, it is important to understand viral versus non-viral systems, as they are two distinctly different approaches to gene delivery.
Viral vectors are built using modified viruses, not the actual virus itself. The most common approach in FDA-approved gene therapies, viral vectors utilize only the parts of a virus blueprint that will allow the therapy to deliver genetic material. Although they offer high transduction efficiency, the drawback to viral vectors is that they can potentially trigger immune responses. AAVs are viral vectors.
Conversely, non-viral vectors require physical or chemical methods for genetic material delivery, such as using a needle to inject something into a cell. Non-viral vectors tend to have a lower risk of triggering immune responses and insertional mutagenesis compared to some viral vectors because they don't involve viral components, but can be less efficient.
Understanding AAV Gene Therapies
Adeno-associated virus (AAV) has been discovered to be an effective tool in gene therapies, as it acts as an efficient method of delivering genetic material into cells, or other living tissue. It contains a single-stranded DNA genome.
There are various delivery systems being used within gene therapy currently, including messenger RNA (mRNA). What makes AAVs unique is that it is often considered safer, as AAVs cannot replicate in the body without external help, and are not known to cause disease in humans. Additionally, they are able to infect a range of cell types, making them applicable in a wider range of treatments.
Due to these factors, AAVs are often considered one of the safest delivery vehicles for in-vivo gene therapies (gene therapies performed within a living organism).
Another unique factor of AAVs is that they are one of the only types of viruses that can be safely transduced into the central nervous system when a treatment requires delivery there. This helps to open the door to treatments for diseases like Parkinson’s and Alzheimer’s. However, as we continue to work with AAVs, researchers are discovering more and more ways that they can help us rethink the possibilities of gene therapies.
How Do AAVs Work?
As small, non-pathogenic viruses, AAVs work by releasing their DNA payload after attaching to a cell and being taken inside, which delivers the information into the cell’s nucleus, allowing it to express the delivered function.
The AAVs used in cell and gene therapies often need to have their genomes altered, so that all viral genes besides those that flank the deliverable DNA are removed. These are then referred to as recombinant AAVs (rAAVs), which have more room for the desired genetic cargo to be introduced prior to delivery.
Current Applications & Companies Leading the Way
There are multiple companies that have FDA-approved therapies utilizing AAV gene therapies as delivery vehicles.
Approved in 2019, Novartis’s Zolgensma® is a gene therapy that utilizes AAVs. It treats patients less than 2 years old with spinal muscular atrophy (SMA), which also has biallelic mutations in the SMN1 gene. In order to deliver the therapy, a vector made from a virus called AAV9 is used.
BioMarin Pharmaceuticals received FDA approval for their treatment, Roctavian, in June of 2023. It is made to treat adults with hemophilia A, specifically those who do not have antibodies to the virus AAV5.
Other notable approved gene therapies utilizing AAVs include Hemgenix from CSL Behring, and Elevidys from Sarepta Therapeutics.
Challenges and Limitations of AAV Gene Therapies
AAVs give us a glimpse into the promising capabilities of the future of gene therapies. However, having only been discovered in 1965, and only having the first FDA-approved AAV therapy in 2017, AAVs are relatively new in the biopharmaceutical world. As with many other new technologies and therapies, this presents some potential pitfalls as AAVs change and evolve.
Firstly, equipment is adjusting to accommodate the needs of emerging therapies like AAVs, but most of the concentration devices currently available on the market are not able to accommodate the small volume, high concentration requirements of AAV vectors.
Additionally, if done incorrectly, operators could also increase host cell contamination during the concentration process. High levels of contaminants can result in immune responses, degraded product stability, or major regulatory concerns. This increases time spent on therapies, as high volumes of contaminants would be detrimental to the overall therapy.
A major challenge of AAV gene therapies is that a significant portion of the population has a likelihood of having been exposed to wild-type AAVs. In these cases, individuals may already have developed antibodies to various AAV serotypes. This could render the therapy completely ineffective.
In order to avoid individuals from receiving a therapy that will not work on them, most gene therapies involving AAVs require a screening for existing antibodies. Although this prevents an individual from paying for a therapy that will not work for them, the preemptive screening can be costly and time-consuming as well.
Finally, like most gene therapies, accurate delivery of AAV gene therapies can be challenging as well. Gene therapies require specific and precise delivery, and off-target transduction has not been completely eliminated within these therapies.
An incorrectly delivered therapy can lead to unintended or harmful side effects, or reduced efficacy. Researchers are continuously working on ways to ensure AAV gene therapies are delivered accurately every time.
Emerging Trends & the Future of AAV Gene Therapies
According to BioSpace, the adeno-associated virus gene therapy market is expected to reach a value of $107.2 billion by 2035, a large jump from the recorded value of $2.7 billion in 2024. That gives us a projected compound annual growth rate (CAGR) of 40.03% from 2025 to 2035.
With over 250 clinical trials of AAV gene therapies happening globally, we can expect to see a much wider range of these treatments on the market in the coming years. Ideally, the combination of efficiency and improved safety that AAVs provide will allow us to more effectively treat disorders and diseases in the future.
Stay Ahead of Emerging Biopharma Trends with HPNE
In our rapidly evolving industry, it is important to stay up to date with the latest information and technologies. At HPNE, a Getinge company, we not only strive to make sure you have access to the newest and most innovative bioprocess solutions, but also to keep you informed about the latest advances in the industry.
To stay informed about the latest industry trends, keep up with our latest blog articles on our website’s blogs page.
Additionally, to learn what bioprocessing solutions may be best for you - whether you are developing an AAV solution, are in the middle of the drug discovery process, or are in full-scale commercial manufacturing - reach out to one of our experts at info@hp-ne.com, or reach out on our contact us page.
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About HPNE
As the industry needs grow, High Purity New England, Inc. continues to supply the biopharmaceutical industry with a range of innovative products, from drug discovery and development to fill-finish, including their flagship product, custom single-use assemblies, as well as pumps, sensors, bioreactor systems, storage and handling solutions and other single-use solutions. Along with their own manufactured products for the global market, they are also a distributor for more than 18 brands in North America.
