Update from Dr. David Clark: COVID and Gene Therapy

Written by: David Clark, PhD, chair of the Coalition for Hemophilia B

There seems to be a lot of concern in the hemophilia community that receiving either of the two adenovirus-based COVID vaccines could prevent you from being eligible for gene therapy in the future. This is not true. 

Both the Johnson & Johnson (J&J) and  AstraZeneca/Oxford (not yet approved in the U.S.) vaccines use adenoviruses to deliver their DNA to cells. The gene therapy treatments currently being developed are using adeno-associated viruses (AAV) to deliver their DNA. In spite of their similar names, adenoviruses and AAV are very different viruses. Antibodies against adenoviruses do not react with AAV. There is no danger that taking an adenovirus-based COVID vaccine will keep you from being able to receive a gene therapy treatment in the future.

Note also that adenoviruses are very common. We have all been exposed to them. They are one of the many types of virus that cause the common cold. Therefore, whether you get an adenovirus-based vaccine or not, you already have antibodies against them.

There is no danger that taking an adenovirus-based COVID vaccine will prevent you from being eligible for gene therapy treatment in the future.

In addition, the idea that having preexisting antibodies to AAV will preclude you from receiving AAV gene therapy is becoming obsolete. At the 2021 European Association for Haemophilia and Allied Disorders  (EAHAD) Annual Congress, uniQure presented results from its Phase III clinical study showing that there was no difference in response to its AAV5 gene therapy among subjects with or without preexisting antibodies to AAV5. (1)

Another related misunderstanding is that the vaccines can cause genetic changes in the recipient. That is also not true. In order to cause genetic changes, the DNA (J&J and AstraZeneca vaccines) or RNA (Pfizer and Moderna) would have to get into the nucleus of the cells. That doesn’t happen. The nucleus is very highly protected. The DNA/RNA is only deposited into the main body of the cell, not the nucleus. In the cell, the DNA/RNA is used to produce copies of the coronavirus spike protein and then is quickly degraded. The body doesn’t like having stray pieces of genetic material, DNA or RNA, hanging around. It is full of nucleases (enzymes that break down nucleic acids) to take care of that.

A related misunderstanding is that the COVID vaccines can cause genetic changes. That is not true. 

It is important for everyone who can to get the COVID vaccines to protect yourself and those around you.  The risk of death and disability from  COVID is much, much greater than the risk from the vaccines. The virus is rapidly mutating to become even more dangerous, and if we don’t get it under control, we could have an even worse problem in the future. Please get vaccinated and continue to wear your mask.

Reference:
1. EAHAD abstracts ABS043, ABS089, and ABS100, Wiley Online Library, February 2, 2021.

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