Researchers circumvent the body’s defence mechanism by combining two IBN innovations

Researchers have successfully circumvented the body’s defence mechanism by combining two innovations from the Institute of Bioengineering and Nanotechnology.

One of the major challenges in virus-based gene therapy is avoiding detection by the human immune system. Researchers are often flummoxed by how to circumvent the internal system which results in the virus not being deactivated before it reaches the intended target.

However, researchers at the Institute of Bioengineering and Nanotechnology have advanced upon two earlier innovations at the research facility and successfully manoeuvred around the body's defence mechanism.

They showed that cancer cells are more adequately eliminated when therapeutic viruses were encased in microfibers or synthetic tissue fibres. Using a method developed at the research facility, they encapsulated an insect virus with fibres produced from peptides and DNA for gene delivery.

Because the structure of the microfibers are very similar to human tissue fibres, they managed to ‘disguise’ the virus by reducing the body’s ability to recognize the virus and prevent its premature deactivation.

Research on mice with brain tumours revealed that the microfiber-coated viruses could significantly slow down tumour growth and prolong survival, in comparison to treatment with uncoated viruses. The researchers used a technique developed by Dr Andrew C. A. Wan at IBN to prevent the body from disabling the virus before it reaches the diseased cells.

The team, led by Dr Shu Wang, used a water-based chemical process to construct tissue fibres from biomolecular materials – peptides and DNA. They flanked two droplets of the oppositely charged peptide and DNA molecules after it has been dissolved in water. Once contact had been made, the droplets zipped together to form a two-component fibre, which is likely to occur from the electrostatic interaction.

Baculoviral vectors were added by the same procedure to coat the virus with the fibres. Dr Shu Wang said: "For the very first time, we have shown that two biomolecules, namely peptides and DNA, can interact with each other to form structured fibers in a test tube. Since these biomolecules are readily metabolized in the human body to naturally occurring molecules and have no adverse toxicity, they hold strong biomedical potential for the delivery of therapeutic drugs, genes, proteins and viruses to combat cancer.

"This innovative application of microfibers with viral vectors is an exciting development for gene therapy that was made possible through multidisciplinary collaboration between biologists, chemists and materials scientists at IBN."

Posted by Neil Clark