In the realm of medicine, RNA (ribonucleic acid) has emerged as a beacon of promise, offering unprecedented opportunities for treating a wide range of diseases. Its versatility, coupled with the remarkable advancements in RNA-based therapies, has ushered in a transformative era in healthcare.In the realm of medicine, RNA (ribonucleic acid) has emerged as a beacon of promise, offering unprecedented opportunities for treating a wide range of diseases. Its versatility, coupled with the remarkable advancements in RNA-based therapies, has ushered in a transformative era in healthcare. mRNA Vaccines: A Triumph in the Fight Against Disease The COVID-19 pandemic brought mRNA vaccines to the forefront of global attention. These vaccines, developed by Moderna and Pfizer-BioNTech, empower cells to produce the SARS-CoV-2 spike protein, enabling the immune system to recognize and combat the virus effectively. Their superior safety, efficacy, and cost-effectiveness have revolutionized the field of vaccinology. Broader Applications in Cancer Treatment Beyond infectious diseases, mRNA vaccines are also proving invaluable in the fight against cancer. By providing cells with instructions to build specific proteins, these vaccines train the immune system to identify and destroy cancer cells without harming healthy tissues. This approach offers both prophylactic and therapeutic options, potentially enhancing survival rates for cancer patients. Protein Replacement Therapy: Addressing Genetic Disorders In cases where cells lack the capacity to produce functional proteins or harbor defective versions, mRNA therapies can intervene. By delivering the correct instructions, these therapies enable cells to produce normal proteins, alleviating debilitating symptoms associated with genetic disorders like cystic fibrosis. Silencing RNA: Suppressing Unwanted Proteins Silencing RNA (siRNA) acts as a molecular gatekeeper, preventing the production of harmful proteins. By targeting and destroying specific mRNA, siRNA can alleviate conditions like familial amyloid polyneuropathy, a rare hereditary disease. Overcoming Challenges and Embracing a Bright Future The development of RNA therapies has been marked by significant challenges. However, breakthroughs such as lipid-nanoparticle delivery systems have paved the way for more precise and effective treatments. As research continues to unravel the full potential of RNA, countless therapies are in development, targeting a vast spectrum of diseases. Conclusion RNA-based therapies represent a transformative force in modern medicine. Their versatility, precision, and potential to address a wide range of diseases hold immense promise for improving human health. As research advances, the future of RNA therapies is incredibly bright, offering hope and innovation for patients around the globe.
It was a matter of perfect timing.
Scientists had been researching the use of RNA for medical purposes for more than 40 years when the COVID-19 pandemic broke out in 2020.
They had already had some success with an RNA therapy that was approved in 2018 to treat people with the rare inherited disease familial amyloid polyneuropathy.
But the use of RNA in the widely used COVID vaccines from Pfizer-BioNTech and Moderna places the molecule on a much bigger stage.
RNA stands for ribonucleic acid. Think of it as the spin-off of the better-known DNA, or deoxyribonucleic acid.
All humans naturally have RNA in their cells. The molecule is vital for the daily maintenance of healthy cells and acts as the cell’s internal messaging system.
RNA is a set of instructions given by DNA, which is the boss, so to speak, in the cell’s headquarters – the nucleus. These RNA instructions are sent down to the cell’s factory floor – the cytoplasm – so that the cellular machinery can follow them.
In the field of RNA-based therapies, scientists can write their own instructions for cells to follow.
The different types of RNA make it possible to develop different types of therapies.
The type of RNA that people are most familiar with is probably messenger RNA, abbreviated as mRNA.
mRNA is a type of coding RNA. Think of it as an instruction manual that teaches a cell how to build a specific protein, similar to what you would get to build flat-pack furniture like a desk or a bookcase.
mRNA therapies include the COVID vaccines from Moderna and Pfizer-BioNTech. These vaccines give cells a blueprint to make their own copy of the SARS-CoV-2 spike protein, training people’s immune systems to recognize and defend against the virus.
The reason mRNA vaccines are so highly praised is that they are often cheaper and faster to produce than traditional vaccines, and they are generally safer and more effective at generating an immune response.
mRNA vaccines are not limited to fighting infectious diseases
A vaccine is basically anything that trains the immune system to fight something.
In cancer, mRNA vaccines provide instructions to make proteins that teach the immune system how to find and destroy cancer cells without damaging healthy cells around them.
MSK mRNA pancreatic cancer vaccine trial shows promising results https://t.co/NZ9SxRg3KA
— Association for RNA Therapeutics (@RNA_Therapeutic) May 30, 2023
These vaccines can be either prophylactic (given to healthy people to prevent certain types of cancer) or therapeutic (given to cancer patients to help the body fight certain types of cancer). This is because, unlike other diseases, cancer patients sometimes cannot mount a sufficient immune response on their own.
Despite the complexity of cancer, several mRNA-based vaccines are currently being tested in humans.
This includes Moderna’s mRNA vaccine against melanoma, which is currently in phase three clinical trials for use in combination with Merck’s approved cancer drug, Keytruda, which teaches the immune system to selectively kill tumor cells.
Moderna and Merck have announced that when messenger RNA (mRNA) technology is combined with the cancer immunotherapy drug pembrolizumab, it creates a vaccine that has been shown to be effective against melanoma. https://t.co/M2y5VU6zSP photo.twitter.com/tWDsY9Hjbz
— Melanoma Research (@MelanomaReAlli) January 11, 2023
BioNTech, in collaboration with Genentech, has an mRNA vaccine in phase two human trials to treat colorectal cancer. And the University of Florida is conducting a phase one clinical trial for an mRNA vaccine to target the most common type of brain tumor.
If even one of these vaccines is successful, it will mark the beginning of a new generation of cancer treatments that will hopefully improve patients’ chances of survival.
Besides vaccines, mRNA can have as many functions as are encoded in its biological coding.
One of the applications for which mRNA is being developed is protein replacement therapy.
Sometimes cells do not have the capacity to make mRNA for a specific protein themselves, or the instructions they have are incorrect, causing non-functional or toxic forms of the protein to be accidentally made.
This is the case in certain genetic conditions, such as cystic fibrosis, in which cells produce a faulty copy of a protein called cystic fibrosis transmembrane conductance regulator (CFTR). This protein causes an unhealthy buildup of mucus in the lungs.
By regularly supplying the cells with the correct mRNA, they can start producing the normal protein.
RCT2100, an mRNA drug for cystic fibrosis developed by ReCode Therapeutics, is one of several mRNA drugs currently being tested in humans for this application.
ReCode Therapeutics Raises $80M to Advance RNA Treatment for Cystic Fibrosis https://t.co/035sUv31hn #ReCodeTherapeutics #RNATreatment #CycticFibrosis #LungDisease #Risk Capital
— Haybury (@Hayburysearch) March 28, 2020
This involves delivering an inhaled form of mRNA into lung cells to help them produce healthy CFTR proteins. The goal is to reduce the buildup of thick mucus and relieve symptoms in patients with cystic fibrosis.
If successful, such mRNA therapies could address unmet clinical needs and the lack of effective treatments, particularly for people with rare genetic disorders.
Another type of RNA is silencing or small interfering RNA, abbreviated as siRNA. This is a type of non-coding RNA, meaning it cannot instruct a cell to build a protein.
siRNA is essentially a kind of gag order, designed to stop the production of defective or unwanted proteins.
siRNA instructs the cell’s machinery to seek out and intercept all copies of a specific mRNA ready for delivery, then rips the copies in half before they can be read by the cell’s production systems.
This leaves the cell with unfinished instructions that cannot be built further, so the mRNA is discarded.
For example, patisiran is an siRNA therapy that was approved in 2018 to treat the rare hereditary disease familial amyloid polyneuropathy. The drug instructs cells to stop making a defective, toxic form of the protein transthyretin.
Many challenges overcome
Over the past 30 years, scientists have faced numerous challenges in developing RNA therapies.
One of the most important breakthroughs is the development of the lipid-nanoparticle delivery system – a synthetic ‘shell’ for the RNA instructions, which protects it from the harsh conditions in the body and allows for more precise delivery to target cells.
This has greatly expanded the field of RNA therapy.
By the end of 2023, more than 80 mRNA therapies were in human trials, at least five new clinically approved mRNA drugs were on the market, and many more were in regulatory approval.
And that’s not to mention the countless therapies in preclinical development by hundreds of companies and academic institutions around the world, and the drugs being developed using other types of RNA.
While there is still room for improvement, the future looks bright when it comes to RNA therapy.
Dr Emily Pilkington and Dr Rekha Shandre Mugan are project managers for mRNA Core, a collaborative initiative to advance the development of mRNA therapies for clinical application. They have received funding for their research from the National Health and Medical Research Council (NHMRC) and the Medical Research Future Fund (MRFF).
Originally published under Creative Commons by 360info
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