New process to ‘program’ cancer cell death created

WASHINGTON - Scientists have engineered a fundamentally new approach to killing cancer cells.

Niles Pierce at the California Institute of Technology (Caltech) has developed the process that uses small RNA molecules that can be programmed to attack only specific cancer cells; then, by changing shape, those molecules cause the cancer cells to self-destruct.

In conventional chemotherapy treatments for cancer, patients are given drugs that target cell behaviours typical of-but not exclusive to-cancer cells.

A better method is to create drugs that can first distinguish cancer cells from healthy cells and then, once those cells have been spotted, mark them for destruction; in other words, to produce molecules that diagnose cancer cells before eradicating them, said Price.

This type of therapy could do away with the side effects associated with conventional chemotherapy treatments. It also could be tailored on a molecular level to individual cancers, making it uniquely specific.

It employs hairpin-shaped molecules known as small conditional RNAs, which are less than 30 base pairs in length. (An average gene is thousands of base pairs long.)

The researchers’ method involves the use of two different varieties of small conditional RNA. One is designed to be complementary to, and thus to bind to, an RNA sequence unique to a particular cancer cell-say, the cells of a glioblastoma, an aggressive brain tumour.

In order to bind to that cancer mutation, the RNA hairpin must open-changing the molecule from one form into another-which, in turn, exposes a sequence that can spontaneously bind to the second type of RNA hairpin. The opening of the second hairpin then reveals a sequence that binds to the first type of hairpin, and so on.

In this way, detection of the RNA cancer marker triggers the self-assembly of a long double-stranded RNA polymer.

As part of an innate antiviral immune response, human cells defend against infection using a protein called protein kinase R (PKR) to search for long double-stranded viral RNA, which should not be present in healthy human cells.

If PKR indeed detects long double-stranded RNA within a cell, the protein triggers a cell-death pathway to eliminate the cell.

“The small conditional RNAs trick cancer cells into self-destructing by selectively forming long double-stranded RNA polymers that mimic viral RNA. There is, however, no virus.

“We used three different pairs of small conditional RNAs, with each pair designed to recognize a marker found in one of the three types of cancer.

“The molecules caused a 20- to 100-fold drop in the numbers of cancer cells containing the targeted RNA cancer markers, but no measurable reduction in cells lacking the markers,” he said.

The findings appeared in the Proceedings of the National Academy of Sciences (PNAS). (ANI)