Artificial viruses to improve gene therapy

Viruses are true experts in entering the cells of other organisms to operate their machinery and multiply.

It is a viral ability that, however, biotechnology is learning to use to our own advantage.. For example, modified viruses are already used as gene therapy vectors, which need to be introduced into a patient's cells to correct a certain genetic defect.

Those vectors, however, are still not very efficient in many cases.. Different lines of research try to significantly improve the way in which these 'vehicles' can be used to deliver a specific therapy to cells.

Research published in the latest issue of Nature Communications provides an interesting alternative to achieve this improvement. It is a new artificial vector that, unlike other options, has been developed from phages, the viruses that infect bacteria.

Specifically, the authors of this development, researchers from the Catholic University of America in Washington (USA), have used a phage called T4 to develop a synthetic vector that has a greater capacity than other options to transfer genetic material and proteins and allows to administer large genetic sequences, a necessity in the treatment of certain genetic diseases.

“Transform personalized medicine”

The technology, the authors note in the scientific journal, “has the potential to transform gene therapies and personalized medicine.”

As proof of concept, the researchers generated a viral vector from the phage that was capable of transferring the dystrophin gene into human cells in the laboratory.. The experiment was only conducted in cell lines, not in animal models or humans.

That is the main limitation of the study highlighted by Gloria Gonzalez Aseguinolaza, researcher in the Gene Therapy and Gene Expression Regulation Program and director of Cima Innovation and Transfer at the University of Navarra. “The study lacks data in animals, and that is where the problems are going to be found.. It is a very large and complex vector and it is highly probable that its in vivo efficacy is reduced and induces toxic and immune responses, as occurs with large viruses, which conditions its therapeutic efficacy,” he said in statements to Science Media Center Spain. .

Along the same lines, Miguel Chillón, head of the Laboratory of Gene Therapy in Neurodegenerative Diseases of the VHIR-UAB Mixed Unit, has pronounced. “This is an interesting system, which very well addresses one of the important problems such as the amount of genetic material, but there are still important issues to be resolved, above all and very especially the immune response that can be induced, before that you can even think of using it in humans.

“It is a very good preliminary study that focuses on the creation of a new gene transfer model based on the bacterial phage T4. Scientifically, the article addresses one of the main aspects in the field of genetic transfer, such as the amount of material that can be transferred, which in this case is very relevant”, he stressed to SMC Spain.

“The main advantage it provides is the ability to carry up to 170 kilobases of genetic material, but also proteins, such as those necessary for gene editing.. As for the limitations, there are some very important ones.. Two of them are discussed in the same article at the end of the discussion: the immune response and the possibility of off-target events associated with gene editing systems.. To this I would add the very little ability to maintain a stable expression of the therapeutic gene over time -unless new systems are introduced into the genome that carry these AVVs [artificial viral vectors]- and the specificity of transducing cell types in a efficient, unless new versions are generated with new external 'bridging' proteins”

“The most relevant and difficult to avoid of all the limitations is the immune response that will possibly induce. I would say that precisely for this reason the authors have not shown in vivo experiments in animal models, because with everything they have done, this last experiment would be easy and would give it great relevance,” he concluded.