RNA Therapy Delays Mice Tumor Growth

Researchers have created a new cancer treatment that targets tumors by deluding cancer cells into ingesting a small piece of RNA that inherently prevents cell division.

According to findings by scientists at Purdue University published in Oncogene, where untreated tumors tripled in size during a 21-day study, those receiving the new therapy did not see growth in size.

A particularly modified form of microRNA-34a, a molecule that operates "like the brakes on a car," slowing or stopping cell division, is combined with a delivery mechanism that specifically targets cancer cells in the therapy, which was evaluated in mice models, according to lead author Andrea Kasinski.

The targeted microRNA-34a significantly inhibited the activity of at least three genes — MET, CD44, and AXL — known to promote cancer and resistance to various cancer treatments for at least 120 hours and reduce or reverse tumor growth.

The research reveals that the patent-pending therapy, the most recent development in more than 15 years of research into using microRNA to kill cancer, may be efficient both by itself and in combination with currently available medications when used to treat malignancies that have developed drug resistance.

MicroRNA-34a is a ribonucleic acid strand, which is a string of ribonucleic acids attached like zipper teeth along the length of a sugar-phosphate chain. The two microRNA strings are unevenly zipped together, with one string guiding a protein complex to the cell's worksite while the other string is destroyed.

Although reintroducing microRNA-34a to cancer cells appears straightforward, the study team faced numerous hurdles in developing an effective therapeutic.

Because naturally existing RNA degrades quickly, the researchers stabilized microRNA-34a by adding numerous tiny clusters of atoms along the length of the strand.

The researchers based their alterations on an FDA-approved chemical structure that Alnylam researchers employed on similar short-interfering RNAs. Experiments on mouse models reveal that the mutated microRNA-34a survives for at least 120 hours after introduction.

The fully transformed microRNA-34a is also undetectable to the immune system, which would typically assault double-stranded RNA delivered into the body.

To guarantee that the mutated microRNA-34a reaches cancer cells, the researchers linked the double strand to a folate molecule.

All cells in the body have receptors that attach to folate and bring it into the cell, but cancer cells, such as in the breast, lung, ovarian, and cervical, have considerably more folate receptors on their cell surface than healthy cells.

The small microRNA-34a and folate combination penetrates tumor tissue and attaches to the cell surface folate receptor. It is then brought inside in a vesicle, which is a small bag of cell membranes. Some microRNA-34a can exit the vesicle once within the cell, slowing cell proliferation.

The therapy's focused specificity decreases the quantity of substance that must be provided to be effective, which reduces possible toxicity, side effects, and expense.