Seeking to overcome the problem of suitable delivery mechanism for gene therapy, scientists at CSIR-Centre for Cellular and Molecular Biology (CCMB) have designed peptide-based delivery platforms for tumour targeting which holds the potential for cancer treatment.

The scientists have developed recombinant peptides through bacterial fermentation to bind DNA or small interfering RNA (siRNA) or short hairpin RNA (shRNA) and deliver them into cells to target tumours. Since DNA, siRNA and shRNA are negatively-charged, they require carriers like recombinant proteins, said Dr. Vijaya Gopal, senior principal scientist, who along with her colleagues designed novel peptide-based carriers to ferry biological macromolecules into cancer cells.

The advantage with DNA or siRNA is that they help in silencing the targeted genes. For instance, if the TF gene involved in new blood vessel formation is silenced, the tumour would get regressed. At CCMB, the scientists designed chimeric peptide by fusing three peptide modules to deliver DNA or shRNA for regressing tumours.

In animal studies carried out in mice, it was found that the novel chimeric proteins had effectively delivered therapeutic nucleic acids and silenced the genes implicated in breast and ovarian cancers. “The tumours had regressed. That’s what we found,” added Dr. Vjiaya. She says the findings hold “very good potential for gene therapy.”

Lack of suitable delivery platforms is impeding progress in gene therapy, she says. While stressing that the main concerns in gene therapy are toxicity and safety, she points out that peptide and lipid-based polymers are two main types of non-viral carriers. Although the suppression of tumours in animal studies has been successful, further investigations are essential to validate the efficacy in preclinical situation, she adds.

Chimeric proteins with different functional properties can be derived from any organism or a virus and produced in bacterial factories using standard practices of recombinant DNA methodologies.

The benefit of using chimeric proteins is that they could be changed to target different tumours. Efforts in this direction are underway at CCMB to evolve peptide-based platform technology with other homing ligands recognising different targets.

Focus areas

One of the focus areas in the future will be to design peptide-based modules to target brain tumours by crossing the blood-brain barrier.

According to CCMB Director, Dr. Ch. Mohan Rao, complete understanding of the physiochemical properties of nanoparticles as delivery systems, including peptides, is essential to improve clinical usefulness.

Targeted drug delivery would be less toxic as it attacks only the diseased cells and spares the normal cells, he says. Drugs may be packaged into small particles made from biodegradable synthetic polymers or designed peptides.

Scientists at CCMB are attempting to study and develop such systems. “In addition to delivering RNAi and DNA, we are also investigating such systems for cancer treatment and conditional-release systems for ophthalmic applications,” he notes.

The future of medicine is likely to depend on targeted and controlled delivery of therapeutic molecules which will make the drug more effective with minimal or no side effects, he says.