Vectors for gene therapy: new approaches needed

By Tuyen Ong, CEO of Ring Therapeutics, CEO-Partner of Flagship Pioneering

Gene therapy is a class of life-changing medication that can treat patients with diseases that were once incurable.

Although revolutionary, significant limitations remain for the vectors that carry them.

Viruses are skilled at delivering genetic material to the nuclei of the organisms they infect, and because of this, they were the first vectors developed for gene therapy delivery. A large number of viral vectors are entering the gene therapy arena including lentiviruses, retroviruses, herpes simplex virus, adenoviruses, and adeno-associated viruses. Each of these candidate vectors is highly immunogenic, recognized quickly by the immune system and cleared from the circulation – leaving antibodies specific to this virus to watch over the body for potential subsequent infections.

Developing novel approaches to construct viral vectors for gene therapy

While this process is ideal for natural viral infections, it poses a problem for viral vectors carrying a therapeutic payload.

Innovation to engineer first-generation viral vectors has been ongoing for decades with gradual success. The therapeutic genetic cargo, however, has advanced rapidly. Developing new approaches to building viral vectors to carry the next generation of drugs is more necessary than ever as many enter the clinic and elicit a toxic immune response.

Sequencing human viromes

One of the key innovations to address this need was driven by a shift in focus in the field of virology. To date, scientists have characterized most of the viruses associated with disease. But what if there is a virus that the immune system doesn’t recognize, that is familiar to us? Human virome sequences reveal the existence of a family of commensal viruses that have lived in the human body for thousands of years called anelloviruses.

Anellovirus is the most common commensal virus in humans. They are present in many tissues throughout our bodies, and they don’t elicit a strong immune response. Because they live inside the human body without causing harm or harm to one’s health, they are promising vectors with great potential for genetic medicine.

In this largely stagnant area of ​​research and development, anellovirus brings hope for the future of the field. The need to build a delivery toolbox for these genetic drugs will continue to grow.

We owe it to our patients and society to rework existing tools and think outside the tool box, seeking entirely new approaches to reshaping what is possible in genetic medicine.