Despite the remarkable advances in the diagnosis and treatment of various types of cancer, combating the disease is still complicated. A research team from Royal Melbourne Institute of Technology (RMIT) Australia, has developed a relatively inexpensive and safe therapeutic technology targeting cancer cells, which can be employed against other human diseases too.
The team designed strategies based on gene therapy to tackle prostate cancer, a common disease afflicting men. Gene therapy involves the replacement, correction or shutdown of malfunctioning genes in our DNA. The RMIT researchers used CRISPR/Cas9 gene editing technology as one of their corrective strategies. Cas9 is a protein with the ability to cut through DNA and the researchers used this function to scramble and shutdown the RPSA gene, whose overtime work in cells causes them to turn cancerous.
Gene therapy is gaining acceptance as a promising alternative to traditional cancer treatments such as surgery, chemotherapy, radiotherapy, hormone therapy or a combination thereof. It minimises a patient’s repeated exposure to the hazardous chemicals and radiation, and is designed to behave as a sustained cure. CRSIPR/Cas9 based therapy targeting various diseases has been used successfully within labs and in certain clinical trials.
The most prevalent method to deliver corrective gene therapy cures is via viruses. Researchers have hijacked the potential of viruses to infect our cells by engineering them to carry any genetic material of choice. The neutered viruses can transport the cure to diseased cells.
A major concern regarding the use of viral vehicles is the reaction of our immune system, which could activate against the micro-transporters and render the therapy useless. “An effective non-viral method would be safer for patients and could significantly reduce the time and expense involved in bringing new treatments to market,” says Dr. Shukla.
To tackle this problem, the researchers in collaboration with Dr. Cara Doherty of The Commonwealth Scientific and Industrial Research Organisation (CSIRO), Australia, developed suitable non-viral delivery vehicles, called metal-organic frameworks (MOFs). “These are biocompatible, minuscule delivery systems, with the capacity to carry genetic load to their targets,” explains Dr. Ravi Shukla, Associate Professor at RMIT, Australia.
MOF’s have been gaining ground in various fields of science due to their immense versatility. They are porous materials made up of metal ions that are connected by organic linkers. MOFs have been designed to self-assemble and can be tuned as per convenience. In addition, they are relatively safer and non-toxic to the patient.
Towards this, Dr. Shukla’s team used ZIF-C, a type of MOF to deliver their CRISPR/Cas9 based gene editing therapy. According to Arpita Poddar, the lead author of the paper, their strategy employed Cas9, a protein that cuts through genetic material, to stop the functioning of the RPSA gene. The shutdown of this gene’s expression in cancerous prostate cells caused a sharp increase in their death in comparison to non-cancerous cells, thus clearing out the diseased cells.
Having solved the logistics problem and observed the effects of the delivered therapy on cancerous cells, the team moved on to their next agenda. How to maximise the cells ability to accept the cure when cells have a tendency to obstruct the entry of foreign objects? Arpita explains that they tackled this issue by coating the MOFs with a compound found in green tea. This plant-based chemical possesses anti-cancerous and anti-oxidant properties. To their delight, the MOFs coated with the green-tea compound had increased entry into the cancerous cells in comparison to uncoated MOFs. The improved uptake of the MOFs aided the shutdown of the over-working RPSA gene and led to a surge in the death of cancerous cells.
“For the first time, we show that the MOF, ZIF-C, is a successful delivery system for gene therapy,” says Arpita. Though her team focused on prostate cancer cells for this study, she states that their work can be utilised to combat various other cancers, diabetes, heart diseases and cystic fibrosis. “Specifically, for now, we are targeting other forms of cancer such as breast, ovarian and cervical,” she adds.
Their pilot study, published in Chemical Communications, has helped MOF biomaterials to make a mark as affordable, non-toxic, therapeutic agents with prospective multi-disciplinary appeal.
# Note: In addition to the quotes sourced from the RMIT press release, the first author, Arpita Poddar was contacted for comments.
A version of this article was published on the Science Media Centre IISER Pune’s blog.
# Cover photo: Bio-art of polymer-based delivery vehicles (gold cubes) transporting drugs to breast cancer cells Credit
