TORONTO – The story of how groundbreaking mRNA vaccines were developed to help the world fight COVID-19 is a fascinating one – but it’s missing a vital part, according to a scientist who says these vaccines have a fundamental Aspect was originally developed by a small team in Canada.

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How mRNA vaccines work, produced by companies such as Moderna and Pfizer-BioNtech, is that the mRNA itself is wrapped in a protective shell made of lipid nanoparticles to allow it to enter the body and teach the immune system how to fight off the novel coronavirus.

Without this important delivery system provided by lipid nanoparticles called LNPs, vaccines would not work.

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But the question of where this system developed – and by whom – is not straightforward.

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Canadian scientist Ian McLachlan is watching the rollout of the vaccine with awe, knowing that he and his team played a key role in their development, which began decades ago.

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“There is a part of me that is almost overwhelmed, how effective and powerful these vaccines are,” MacLachlan told Granthshala News in an interview.

“There would be no mRNA vaccines without the LNP system that was developed right here in Canada.”

MacLachlan was featured in a recent Forbes investigation, Those who are caught in a tangled web of scientific works, patents, companies and lawsuits surround the issue of who deserves credit for LNP, and in particular, whether LNP is used in COVID-19 vaccines.

MacLachlan said many people believe mRNA vaccines came out of nowhere, but that the technology has been in the works for years.

“I’ve had conversations with people who imagine they were developed within the past 12 to 18 months,” he said. “But in fact, soon after the discovery of nucleic acids and their role in biology, people started thinking about ways to use nucleic acids as medicine.

“The idea of ​​using RNA as a vaccine is something that’s been around for 20 or 30 years.”

A team of dedicated scientists in Vancouver was part of it. They knew the world would need new tools to fight diseases, and were determined to develop some.

“We wrote the script for this film,” McLachlan said. “We saw it coming. We know these are emerging infectious diseases that are out there. And we need to prepare for them as a society. And one way to prepare for them is that we and to make them available as widely as possible, so that when that time comes, they are available for use by our societies.”

In the early 2000s, scientists were honing in on the therapeutic potential of RNA. But for RNA-based drugs to work, they need to be delivered in a way that allows it to enter a cell.

Over the coming decade, MacLachlan and a team from Protiva, which he founded, worked on that problem, and figured out a way to deliver RNA safely. They found that a specific ratio of the four lipids formed the delivery system necessary to envelop the RNA, protect it, and bring it into the cell.

Mark Kay, a professor of genetics at Stanford University, became aware of MacLachlan and his team’s work in the field when they were looking into siRNA, a therapeutic method that uses RNA to turn off certain genes.

“It was clear from the work that he was doing that he had indeed discovered something extremely important that would allow these RNAs to be delivered therapeutically, as well as safely, and eventually to humans,” Kay told Granthshala. News.

He explained that while other scientists were working in that area when it came to delivery systems that could be used safely in humans, MacLachlan and his team’s method stood out.

“Clearly the innovation that went into these lipid nanoparticles” […] I think that is a game changer,” he said.

“What he and his colleagues contributed is a very, very important breakthrough that ultimately led to the early successes of the delivery of RNA in humans.”

But this contribution from Canada has not been highlighted since the start of the pandemic and during the whirlwind race to develop these innovative new vaccines.

In a recent article calling MacLachlan the “forgotten hero of Covid”, Forbes revealed the Canadian side of the story after finding MacLachlan’s name at the center of a patent linked to the origins of the LNP delivery technology.

“I think it’s great that she’s getting the recognition that she’s in for it, because it was important,” Kay said.

Looking back now, MacLachlan said there are many reasons to appreciate Canada’s contribution to LNP and mRNA vaccines.

Part of this is that when scientists tackle a problem, their new discoveries are based on existing data and discoveries from those that preceded them, which means that sometimes the focus is only on the most recent developments.

“There is an incident whereby [the] The last person to have the data wins,” he said.

“To some extent, I think this is by accident. But, at the same time, there is some, shall we say, controversy about the ownership of this technology, and it may play a role.”

The legal entanglement of who owns a technology, or can claim credit for it, complicates the story of mRNA vaccines.

For example, Moderna tried to challenge a patent for LNP technology filed by a Canadian company—a patent with MacLachlan’s name on it—but then, after upholding the existing patent, Moderna stated that its Its technology has evolved far beyond the described technology. Patent.

Preclinical data released by Moderna suggests that their delivery system was composed of similar proportions of the same four lipids that MacLachlan and team used, but In a statement to Forbes in 2020, Moderna said the preclinical formulation was not the same as the final vaccine.

Moderna says they have their own LNP technology in their mRNA vaccine.

But the legal questions about the LNP began long before the pandemic began.

Missed opportunities and legal exhaustion

Kay wasn’t the only scientist who drew attention to the work of MacLachlan and his team at the time.

In 2006, MacLachlan’s work caught the eye of a talented biochemist – Katalin Kariko, a Hungarian scientist who is now at the forefront of the Nobel Prize for his revolutionary work with mRNA.

Kariko has worked with BioNTech since 2013, but long before that, she proposed to MacLachlan that they partner with her to use its messenger RNA with its delivery system.

In an email to Granthshala News, Kariko reported that he had consistently asked her in 2006 to consider using her LNP with mRNA.

“I [knew] that he was preparing the siRNA, and I wanted him to try the mRNA as well,” he said. “Why did I want to prepare the mRNA with the LNP? The mRNA product requires a shelf-life. need[ed] Prepared mRNA that can be stored in the freezer for extended periods of time.”

However, MacLachlan was embroiled in legal conflicts over the technology, and so rejected Cariko’s idea.

“We were a small company at the time, and focused a lot on siRNA drugs, as opposed to mRNA drugs,” he said.

Legal battles played a part, and nearly a decade later followed a “legal wrangling over ownership”. [LNP], “McLachlan was drained.

He said that as the company expanded and there were partners who were “not necessarily very well behaved,” a legal dispute arose with him over ownership of the distribution system.

“It was a very unfortunate distraction, and something I didn’t want to spend the rest of my life with,” MacLachlan said.

So in 2014 he ended up moving away from it all by quitting his job to travel with his family to the Motor House.

MacLachlan is now an independent scientist, consulting with various pharma companies. He has no financial stake in his former company, and receives no royalties from his LNP work, which he says is part of about 10 other vaccines and pharmaceutical products.

But he’s hoping to set the record straight, and is coming forward now that his story is over.

“I don’t have a financial horse in this race, so to speak,” he said. “But I’m also happy to encourage from time to time to help people understand this technology and make it available to as many people as possible who choose to use it.”

One of the main reasons MacLachlan agreed to talk to the media about developing the LNP is that he wanted to uplift his team, not his own work.

“As an independent scientist I no longer have a platform to advertise my team’s achievements,” he said. “It’s an opportunity for me to acknowledge that team and make sure their work is top-notch.”

He said that these vaccines had their roots in Canada long ago.

“We started it to help people, and it’s great to know that we are able to do that,” McLachlan said.

He said that some people may distrust COVID-19 vaccines because they come from big corporations, but there are countless human beings behind these life-saving shots.

McLachlan urged Canadians to take their shot.

“At the end of the day, this technology was developed by young men and women scientists who really wanted to do what they could to help people,” he said.

“That’s where it comes from. It doesn’t come from a faceless multinational corporation. It’s from the hearts and minds of people like me, and hopefully it can help some Canadians.”