New 'hitchhiking' virus has drug delivery potential

By Wai Lang Chu

- Last updated on GMT

Related tags Gene therapy Cancer Immune system

Researchers in the US have constructed a new virus-based gene
therapy delivery system that has uses in cancer treatment. The
findings are said to provide a solution to the problems that have
hampered gene therapy treatments.

The research opens up new opportunities for using viruses therapeutically as this method of attachment allows researchers to not only target particular cells, but also to gain entry more easily into the cells. This must be achieved in order to deliver therapeutic genes to destroy tumours.

The researchers have become the first to exploit traits of retroviruses during the infection process of a cell in which attachment to the cell can occur in a non-specific way.

They concentrated on particles derived from the retroviruses. The viral particles attach to a specific kind of T cell in the immune system and "hitchhike" to the tumour because T cells home in on tumours naturally.

By hitching a ride on the T cells, the therapeutic particles can hit their tumour target while avoiding detection (and destruction) by the immune system.

Using mice, the team from the Mayo Clinic showed that retrovirus particles could successfully attach to the surface of primary T cells and then be carried through the bodies of mice that had fully functioning immune systems, evading detection by the immune system, to reach tumours and the sites of T cell accumulation.

They further demonstrated that once it reached the tumour, the viral transporter successfully transferred a gene to both mouse and human tumour cells that then infected the cells.

"Any clinical situation in which cells home to disease sites - such as inflammation or autoimmune disease - might benefit from this approach,"​ said Richard Vile, Mayo Clinic molecular immunologist and lead researcher of the investigation.

"Our work is an important contribution to the maturation of the field of gene therapy because ultimately treating cancers by gene therapy depends on scientists' ability to specifically target tumour cells in the patient - and this specific-delivery feature has eluded researchers for a variety of reasons,"​ he added.

Vile pointed out that by devising a way for viruses to hitch rides on antigen-specific T cells, the team have been able to get over multiple obstacles to gene therapy.

Vile emphasised that the work was still experimental and not yet ready for use in human patients. But if larger studies validate these findings, the therapeutic hitchhiker approach may be employed in clinical trials of new treatments.

Despite years of research, gene therapy has largely failed to live up to its promise as a targeted, specific and well-tolerated treatment approach.

The primary reason for this is that it has been difficult to deliver the gene to the required areas of the body safely, in sufficient quantities, and in a form stable enough for good expression of the protein for which it codes.

Viruses have been used as delivery vectors but have fallen out of favour somewhat because of toxicity issues, and attention has turned to non-viral alternatives.

While still in its infancy, a market research report published earlier this year by Kalorama has suggested that the nucleic acid therapeutic market, including gene therapy, could in time achieve a value of over $210 billion (€161bn).

The Mayo research team, which includes a collaborator from the United Kingdom, describes its new approach in the current edition of Nature Medicine.

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