They develop artificial viruses for their application in gene therapies

A team of scientists led by the Catholic University of America (CUA) in Washington, USA, has designed artificial viral vectors (AVVs) from viruses that infect bacteria to improve gene therapy processes. These customizable nanomaterials could evade the possible memory of our defenses against them and have a greater capacity.

Viruses are efficient biological machines capable of rapidly replicating and creating offspring. Some human examples, such as lentiviruses, were previously designed to deliver therapeutic DNA or RNA in animals, but their capacity was limited and they presented several safety concerns.

They showed for the first time that a T4 bacteriophage can wrap around a lipid, facilitating the transfer of vital treatments into human cells.

Harnessing viral mechanisms by building AVVs programmed with therapeutic molecules can perform beneficial repairs to help restore human health. This method can be performed at low cost, with high yield. Furthermore, the nanomaterials remained stable for several months, according to the study published in Nature Communications.

The researchers made the AVVs with a virus called bacteriophage T4. These vectors have a large internal volume and a large external surface area for programming and delivering biomolecules in treatments.

Several scientists in lab coats pose in front of the camera.

Venigalla Rao’s laboratory at Rao Lab. From left to right: Wenzheng Guo, Xiaorong Wu, Rao and Jingen Zhu. /Patrick G. Ryan

The founding director of the CUA Bacteriophage Medical Research Center, Venigalla Rao, is dedicated to studying the therapeutic potential of a type of virus that cannot infect humans and many of which are part of the microbiome of a healthy body.

Rao and his group showed for the first time that a T4 bacteriophage can engage a lipid, a breakthrough that facilitates the transfer of vital treatments into human cells.

“The T4 artificial viral vector (T4-AVV) technology platform can be applied to a wide range of genetic diseases such as sickle cell anemia, muscular dystrophy; also in diabetes or cancer”, says Rao to SINC. “We believe we have shown that there is a way to develop safe and effective bacteriophage-based gene therapy treatments with almost unlimited curative potential,” he adds.

This method can be applied to a wide range of genetic diseases such as sickle cell disease and muscular dystrophy.

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Venigalla Rao, study leader

In proof-of-concept experiments, the authors generated AVV loaded with proteins and nucleic acids to demonstrate their use in genomic engineering. The platform was able to successfully deliver the complete dystrophin gene into human cells in the laboratory and perform several molecular operations to remodel the human genome.

The authors believe that this method can be promising in the clinical treatment of rare diseases, but more studies are needed to evaluate its safety. “The T4-AVV technology needs to be further developed with primary human cells isolated from blood before going to the clinic. The technology will also be tested in animal models such as mice and rhesus monkeys”, explains Rao.

Limitations and next steps

One of the most difficult limitations to avoid in in vivo experiments will be the immune response that the bacteriophage can produce.

In this regard, the expert points out that “it is expected that immune responses to the vector will occur, but it will be necessary to evaluate in future clinical studies how this will affect the therapies and how they will have to be adjusted”.

Immune responses to the vector are expected to occur, but how this will affect therapies and how to tweak them will need to be evaluated in clinical trials.

Venigalla Rao

Current research on gene therapy can be classified into three main approaches that are based on the following vectors or vehicles for treatment: adeno-associated viruses and lentiviruses, lipid nanoparticles and synthetic nanoparticles. All of these treatments remain experimental.

“Real therapy is years away, but this work provides a blueprint for developing life-saving treatments and cures,” emphasizes the research leader. “What we are investigating is a type of molecular surgery that can safely and precisely correct a defect and generate therapeutic results. results”.

The ultimate goal, concludes Rao, is that, unlike current small-molecule drugs that sometimes need to be taken for life, a future bacteriophage-based drug “could cure in a matter of hours or days.”

Reference:

Rao, V. et al. “Design of artificial viral vectors based on T4 bacteriophages for human genome remodeling” Nature Communications (2023)

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