A gene-editing technique that modifies messenger RNA (mRNA) to induce an immune response was used for the two COVID-19 vaccines currently being distributed in the U.S. and could revolutionize the creation of future vaccines and medical therapies. Alexa Kimball, MD, MPH (President & CEO, Harvard Medical Faculty Physicians at BIDMC) said people have recognized the possible utility of mRNA for years, but COVID rapidly advanced this research.

Healthline – January 17, 2021

New mRNA Technique Used on COVID-19 Vaccine May Lead to Flu, HIV Vaccinations

• Experts say the mRNA technique used to create COVID-19 vaccines has the potential to revolutionize that industry.
• They say the new technology could help develop vaccines for the flu and HIV.
• The mRNA technique works by recreating a signature feature of a virus and teaching the immune system to attack it.

A novel technology used for the two COVID-19 vaccines that are being distributed in the United States could revolutionize the creation of future vaccines and medical therapies.

More than 100 COVID-19 vaccines are in development or in clinical trials, but the vaccines from Pfizer-BioNTech and Moderna share a common development process.

Each uses a breakthrough gene-editing technique that modifies messenger RNA (mRNA) to induce an immune response.

Following the successful development of the COVID-19 vaccine, Moderna has already announced its intention to develop vaccines for both the flu and human immunodeficiency virus (HIV) using this technique.

“RNA is basically biological code or biological software,” Dr. John P. Cooke, a physician-scientist with Houston Methodist Hospital and an expert in mRNA technology, told Healthline.

“You write the code very quickly and pretty much encode in the RNA any protein that we want the cells to generate,” he said. “If we can get that software into the cell, the cell will follow those instructions and make that protein for us.”

In the case of the COVID-19 vaccine, the mRNA strand is programmed to create the “spike protein” of the novel coronavirus, which induces an immune response that can protect against an encounter with the real virus.

“When the vaccine is injected into your arm, your cells will take it in, ‘read’ the mRNA sequence, and make the spike protein. Because your own body doesn’t have any proteins that look like that spike, your immune system ‘sees’ it as dangerous and mounts an attack against it,” Mary Kay Bates, the senior cell culture scientist at Thermo Fisher Scientific, told Healthline.

“And if you later get infected with the coronavirus, your immune system remembers that spike protein and still has the proper weapons to neutralize it,” she said.

Because mRNA vaccines only need to reproduce a small part of a virus and don’t have to be produced within cells and purified like traditional vaccines, these mRNA-based vaccines can be developed much quicker than previous approaches.

“The core advantages of mRNA-based vaccine platforms are their ability to be rapidly adapted to different diseases, as the production of the target antigen is ‘outsourced’ to host cells, meaning only the genetic sequence of the antigen needs to be known to design a vaccine candidate,” said Michael Haydock, a senior director at Informa Pharma Intelligence, a pharmaceutical analytics and marketing firm.

How fast?

The time between the Chinese government sharing their genetic sequence of SARS-CoV-2 and Moderna shipping its vaccine candidate to the U.S. National Institutes of Health (NIH) for phase one trials was just 44 days, Haydock told Healthline.

History of the technique 

While this mRNA technique has won sudden global attention, the process has been researched and developed for nearly 30 years.

“There are three major advances that have made the Moderna, the Pfizer-BioNTech, and similar vaccines for the SARS-CoV-2 virus possible,” Bates said.

“The first technology is chemistry used in creating the mRNA sequence that makes it more stable (mRNA is quite fragile and easily destroyed), while the second advance is the lipid nanoparticle that coats the mRNA to protect it — this technology was developed in the 1990s,” she said.

The third is the technology used to stabilize a given protein in a virus, such as the spike protein in COVID–19, which was developed around a decade ago.

“Viruses are very tricky and can change their appearance,” Bates said.

“That spike protein changes shape before and after it infects a cell, so the stabilization preserves the ‘travel clothes’ the virus is wearing when it is traveling around the body, ensuring the spike protein from the vaccine looks the same way it does when the virus is most infectious,” she said.

Flu, HIV, and beyond

“People have recognized the possible utility of mRNA for years, but COVID advanced this research really rapidly,” said Dr. Alexa B. Kimball, the chief executive officer of Harvard Medical Faculty Physicians at Beth Israel Deaconess Medical Center in Boston.

Moderna’s research into flu and HIV vaccines will likely use the advantages of the mRNA encoding process in different ways.

“The challenges for flu and HIV are different,” Kimball told Healthline. “For flu, the challenge is keeping up with the strains of the virus as they change. Since mRNA can be easily changed and then rapidly produced, it may help speed new versions of the vaccine.”

“For HIV, the virus is good at hiding from the immune response and there are many different strains, so part of the challenge is finding a piece of it to mimic,” she added. “New versions of mRNA vaccines with stronger signals and amplification might help combat this problem.”

As transformative as a vaccine for HIV and the flu would be, mRNA also has the potential for claiming a brass ring in modern medicine: a cure for cancer.

“Cancers can proliferate, and metastasize and kill you because they evade immune surveillance. That is, they evade the white blood cells that are meant to get rid of cancer,” Cooke said.

“Every cancer is different because cancers are in large part derived from cellular mutations and mutations maybe are often very different from one tumor to another. Every person has their own tumor,” he said.

Scientists using mRNA to treat cancer would sequence a person’s tumor and look for unique surface proteins in the cancer it can instruct the body’s own immune system to attack.

“With RNA it is possible to personalize cancer vaccines,” Cooke said.

A new era of medicine? 

Despite decades of development, mRNA therapies are just now poised to take off.

“mRNA vaccine products had not previously received regulatory approval for use in humans due to general lack of clinical trials conducted for this approach, and logistical obstacles around stability and delivery of products,” Cliodhna McDonough-Stevens, a regulatory life sciences lawyer at Fieldfisher, told Healthline.

“With an increase in mRNA products in the vaccine field, we are likely to see more specific guidance developed to aid in the production and evaluation of new mRNA vaccines,” she said.

In other words, the doors are wide open now for further experimentation and treatment development.

“I think we’re at the dawn of a whole new therapeutic arena,” Cooke said. “It’s going to be a whole new industry and it’s going to give us limitless possibilities for treating diseases that were undruggable. RNA will allow us to treat many that were heretofore untreatable.”