Sanju’s Superhero Story

COVID Vaccines and Gene Therapy

Authors: This statement was modified with permission from a statement written by Veronica Hood, PhD at the Dravet Syndrome Foundation, with edits from Tanya Brown, PhD, Rachel Bailey, PhD, and Brenda Porter, MD, PhD

There has been some worry in the rare disease communities about the approaches that COVID-19 vaccines are using and how they may interact with future gene therapy approaches for specific disorders.

Two of the current vaccines approved in the United States (Moderna and Pfizer) use RNA enclosed in a lipid droplet. The lipid droplet itself has not been shown to create any sort of immune reaction and none of the components of these vaccines remain long-term in your body. The RNA-based Moderna and Pfizer vaccines should not pose any risk to future gene therapy approaches.

Two other vaccines that are approved in the US and/or are being used in other countries (Johnson & Johnson and Astra-Zeneca) use DNA enclosed in an adenoviral vector. An adenoviral vector is basically a modified “shell” of an adenovirus; the virus’s genetic material has all been removed and scientists have co-opted the “shell” to send in genetic material that they want. The components of these vaccines, as the RNA ones described above, will not remain long-term in your body. However, different from the lipid droplet, the adenoviral vector itself can cause your immune system to react. When your immune system reacts to something, it creates a memory of how to best recognize that foreign molecule and quickly remove it. This means there is a potential risk with an adenoviral vector that your immune system would recognize exposure to a future adenoviral vector and react to it.

The genetic therapy that is progressing towards use in a clinical trial (Taysha Gene Therapies, TSHA-105) for the treatment of SLC13A5 Deficiency should not be at risk for an interaction with any of the vaccine approaches discussed above. TSHA-105 (developed by Taysha Gene Therapies) is DNA delivered by an adeno-associated viral (AAV) vector. An AAV vector is derived from a different type of virus than an adenovirus, and the two should not pose cross-immunogenicity risk. So, receiving a vaccine delivered by an adenovirus vector should not create any issues with receiving a gene therapy delivered by an AAV vector (like TSHA-105).

However, there are other groups working on gene therapy options using adenovirus vectors, and they may become a reality in the future. It is possible that the adenovirus vector vaccines could pose a potential risk to a successful genetic therapy approach that uses an adenovirus vector in the future. There are many types of adenoviruses, and many people naturally encounter adenoviruses in the environment and develop some level of immunity, so it is not a certainty that this would necessarily cause an issue. 

While there is still much we do not understand, the take-home is that there is possibly a risk that vaccines delivered with adenovirus vectors (such as Johnson & Johnson or Astra Zeneca’s COVID-19 vaccines) could create an issue with a future gene therapy, but there is at this time not thought to be a risk to the gene therapy that is progressing towards use in a clinical trial (Taysha Gene Therapies). The currently approved RNA-based vaccines (Pfizer and Moderna), are not a concern for any likely gene therapy trial.

 

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