ITMO: Antisense Oligonucleotide Technology for Cancer Therapy

Main article:

• Cancer (cancer)
• Cancer treatment

2022: Announcement of antisense oligonucleotide technology for cancer therapy

On July 26, 2022, representatives of ITMO University announced that it was proposed to use antisense oligonucleotides - synthesized short DNA fragments - to destroy a cancer cell. Researchers have developed a system that allows simultaneously detecting tumor markers in cells and "turning off" genes responsible for tumor survival. The device can be changed for any cancer marker and target gene - this opens up opportunities for an effective fight against oncology.

ITMO scientists have proposed the use of antisense oligonucleotides to destroy a cancer cell

As reported, radiation therapy and chemotherapy are actively used to treat cancer. However, side effects and chemoresistance lead scientists to look for other ways to fight cancer. An alternative to these methods can be gene therapy technology, namely antisense oligonucleotides - single-stranded artificially synthesized short DNA fragments. At the same time, there is a difficulty in using antisense agents as anticancer drugs: they can suppress the right genes in healthy cells.

ITMO University researchers have found a way to solve this problem: they optimized the usual technology of antisense agents so that instead of one target molecule, it recognizes two. To do this, they created a design based on binary antisense oligonucleotides for searching for tumor markers and selective cleavage of malignant formations. The system consists of two modules: sensory, which looks for special nucleic acids that signal the presence of cancer, and a therapeutic, "catching" target molecule that needs to be destroyed. Prior to ITMO scientists, no one considered the technology of antisense agents for the oncomarker-dependent launch of cancer therapy.

This technology allows cancer cells to be killed and healthy tissue left intact. Our construct forms a complex with the target RNA molecule of the gene of interest and the oncomarker. It then interacts with the intracellular enzyme RNase H, which is able to cleave the RNA molecule. We tested the development in the presence and absence of an oncomarker. The system works 6 times more efficiently if available, which means that the cancer marker activates the device to selectively destroy the gene we need. Basically, we want to force the resources of the cell itself to destroy malignancies. told Valeria Drozd, author of the study, engineer of the chemical-biological cluster of ITMO University

The researchers tested the effectiveness of their proposed in vitro solution on an RNA fragment of the GFP (green fluorescent protein) gene. It is widely used as a luminous label in cellular and molecular biology to study the expression of cellular proteins. Scientists chose a fragment of the KRAS gene as an oncomarker. It is represented in many types of cancer. About 27% of cases of cancer in humans are associated precisely with a mutation of the genes of the RAS family.

We destroy the RNA of the GFP gene, which leads to a decrease in the number of fluorescent proteins (the cell begins to glow less). This test is necessary in order not to immediately destroy cells by acting on vital genes. It is important to make sure that the system purposefully turns off the desired gene in the presence of an oncomarker, and not because it is toxic in itself. We also tested the development for mutation recognition in an oncomarker. For example, if mRNA genes (informational RNAs) are taken as such markers, then they can be expressed in both healthy and cancerous tissues. In the latter, they will have a special mutation: one letter in the chain will be replaced by some other. We also need to recognize this letter so that the device responds specifically to tumor cells. Our system is able to detect nucleotide substitution in the tumor marker. Valeriya Drozd explained

The design proposed by scientists can be modified for any system, any cancer marker and target gene - this opens up opportunities for future research.

Ahead of the researchers is serious work to develop a strategy for the chemical modification of antisense agents. It is important that the defense mechanisms inside living systems do not destroy the structure before it acts on the cancerous tumor. In addition, scientists are trying to identify the most vulnerable survival gene in cancer cells and a universal tumor marker suitable for several types of tumors at the same time.