Proteins are created through the translation of messenger RNA by ribosomes, one amino acid codon at a time. by reading and synthesizing the linear sequence. Membrane transport proteins receptors, antibodies, hormones, enzymes, hemoglobin are mostly composed of protein. It is evident that streamlining and modifying the reading and synthesizing process, would open a massive window of opportunities for the medical ecosystem.
What was done?
A team of biologists and engineers led by James J.Collins developed a new model for RNA therapy with artificial RNA. This model addresses the issue of only allowing affected cells to produce specific proteins for a specific problem without involving surrounding cells, thereby, providing a more accurate intervention with minimum to no side effects.
The team developed a small device that when inserted into a cell, would allow translation to proteins only when viral RNA or a cell-specific RNA is present. Similar to this discovery, this team developed bacteria toehold switches with Peng Yin, in 2014. These switches are in a default off-phase and are only switched on by a specific RNA. When switched on, a protein corresponding to the RNA is synthesized.
This new device called “eToehold device” uses Internal Ribosome Entry Sites (IRES) as a control element. This control element is a sequence in a viral RNA. It allows the host’s protein-synthesizing ribosomes to access a portion of the viral RNA. These now attached ribosomes scan the encoding sequence of the RNA and synthesize the needed proteins. This control element is inserted into the eToehold device, which is programmed to sense pathogen-specific trigger RNAs in humans.
Implications for our world
So many diseases are linked to the translation aspect of the central dogma of molecular biology. From defective DNA producing defective mRNA to pathogens taking control of the body’s protein-synthesizing machinery to even viruses and prions duplicating themselves, an ability to regulate the translation process with finesse will always have multiple applications in human and veterinary medicine.
This research has tremendous importance in gene and RNA therapies. It solves the problem of off-target toxicity which has troubled this field. The eToehold platform could help create therapies that use RNA and protein targeting technology to target specific cells. Also, eToehold has paved a new path in stem cells regeneration. Stem cells can now be triggered to produce specific cell types in the production of vaccines and cell therapies.
In comparison with control RNAs, trigger RNAs together with eToehold sequences have obtained 16-fold induction of fluorescent reporter genes. eToehold has been used to detect SARS-CoV-2 virus RNA, Zika virus RNA, and melanin-related human cells.
The limits of this device are unknown as it can be used in making new RNA from stable DNA molecules. This new RNA is then used to synthesize the specific types of protein needed. This discovery is a relief for medical science, as it births a new approach for developing cures, vaccines, and treatment in plants, humans, and complex organisms.
RNA-responsive elements for eukaryotic translational control