mRNA: How to turn your body into a pharmaceutical biofactory?
In some articles earlier I wrote that the idea of nanorobots as engineered steel machines, but very small ones, is overrated. There is no point in trying to drag something into the body from the outside if we already have internal biorobots, and it would be nice to pump up their potential. The capabilities of mRNA prove this.
Alvin Toffler in his book “Futcroshock” wrote about the moment of rapid accumulation and distribution of products of technological progress. Ray Kurzweil is betting that technological singularity may come in the next 20-30 years. How accurate these dates are – I do not know. But the wave of research in the field of biotechnology, neural networks, implants is only gaining momentum.
The essence of mRNA research
Engineered mRNA transformed cells into tiny biofactories that produce drugs to successfully treat an inflammatory skin disease and two types of cancer. The technology is slowly paving the way for therapies in which the patient's body produces the necessary drugs itself.
What's so interesting about mRNA?
Messenger RNA (mRNA) contains instructions that tell a cell to make a specific protein through a built-in mechanism. Many people know about mRNA because of its connection to COVID-19 vaccineBut mRNA has potential that extends beyond this use, including genetic treatments for a range of diseases.
A recently published study describes an example of such use. Researchers at the University of Texas (UT) Southwestern Medical Center used engineered mRNA to induce cells to secrete their own drugs to successfully treat psoriasis and cancer in mice.
Instead of going to a hospital or outpatient clinic for infusions, this technology will allow the patient to receive a course of treatment with one procedure per month, significantly improving their quality of life.
Daniel Siegwart, professor of biomedical engineering and biochemistry at UT Southwestern and corresponding author of the study.
Such studies look doubly interesting given that it is already quite possible genetic modification of cognitive skills.
Progress in working with mRNA
In working with mRNA, progress has been made in the area of therapeutic delivery using nanoparticles. However, most of the research has focused on getting cells to generate proteins that can be used directly within cells or indirectly trigger pathways that are needed for gene editing. But the researchers have gone further:
The research is about how to extract these important proteins from cells so that they can have a therapeutic effect in other parts of the body.
Inside cells, signal peptides (SPs) act as “metaphorical shipping labels,” as the researchers put it. These labels direct proteins made from genetic instructions to where those proteins are needed.
Some SPs direct proteins to the interior of the cell, such as the nucleus and mitochondria, while others—secretory SPs—expel secreted proteins into the extracellular space.
With this in mind, the researchers hypothesized that the engineered SP could be copied and pasted into the mRNA code to force proteins that are normally restricted to the intracellular space to participate in the external circulation as well.
Use of mRNA in practice
The scientists isolated a piece of mRNA that produces secretory SP, derived from factor VII, a protein involved in blood clotting. They then attached this SP-encoding piece of mRNA to four different mRNA sequences that produced specific proteins:
mCherry, a fluorescent protein that provides a visual clue as to which cells have made new proteins.
Erythropoietin, a human protein involved in blood production.
Etanercept, a therapeutic protein used to treat inflammatory diseases.
Anti-PD-L1, another therapeutic protein used to treat cancer.
When the modified mRNAs were packaged into lipid nanoparticles and delivered to cells in a laboratory setting, the laboratory cells secreted SP-tagged proteins into the fluid outside the cell.
Augmented mouse mRNAs
The researchers used the technology to treat mice with psoriasis, an autoimmune disease that causes inflammation of the skin. The modified mRNA coded for the drug etanercept, and the mice's skin plaques were significantly reduced.
The scientists switched to mice with colon cancer and metastatic melanoma. They used modified mRNA encoding anti-PD-L1. As a result, tumor growth was significantly reduced, and the mice lived twice as long as mice without treatment.
The researchers said the use of Signal peptide Engineered Nucleic acid Design (SEND) technology improves efficacy and helps overcome side effects associated with protein drugs currently administered by infusion.
They said drugs produced using the technology could improve the health and quality of life of patients with inflammatory diseases, cancer, bleeding disorders, diabetes and various genetic disorders.
Who knows, maybe a new technology will be built around this one. model of intelligence?
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