Science New Self Replicating “sa-mRNA Vaccine” Approved For Mass Production - Because "self replicating" just fills you with confidence.

Self-copying RNA vaccine wins first full approval: what’s next?​

Researchers look ahead to the potential uses and benefits of a technology that has been more than 20 years in the making.

Self-amplifying RNA vaccines will add to the arsenal of conventional messenger RNA jabs.
Credit: Pascal Pochard-Casabianca/AFP via Getty

The approval of yet another RNA-based vaccine for COVID-19 might not seem momentous. But the endorsement last week by Japanese authorities of a jab against SARS-CoV-2 constructed using a form of RNA that can make copies of itself inside cells — the first ‘self-amplifying’ RNA (saRNA) granted full regulatory approval anywhere in the world — marks a pivotal advance.

The new vaccine platform could provide potent defence against various infectious diseases and cancers. And because it could be used at a lower dose, it might have fewer side effects than other messenger RNA (mRNA) treatments have.

When used as a booster in clinical testing, the newly authorized vaccine, ARCT-154 — developed by Arcturus Therapeutics in San Diego, California, and its partner CSL, a biotechnology firm headquartered in Melbourne, Australia — triggered higher levels of virus-fighting antibodies that circulated the body for longer than did a standard mRNA COVID-19 vaccine.

Researchers have been trying to make saRNA vaccines a reality for more than 20 years. “Being the first to bring an approval for this platform is pretty huge,” says Roberta Duncan, RNA-programme leader at CSL and vice-chair of the Alliance for mRNA Medicines, an advocacy organization that launched last month to advance the sector’s policy priorities.

“It’s incredibly validating to the field,” says Nathaniel Wang, chief executive and co-founder of Replicate Bioscience in San Diego, California, a company that develops saRNA vaccines. He anticipates that, with continuing advancements, saRNA technology will increasingly replace conventional mRNA in a diverse array of therapeutic contexts. “It has more versatility in its potential,” Wang says.

Amped up​

That versatility emerges from its unique features.

Conventional mRNA-based COVID-19 shots consist mainly of the genetic instructions for a viral protein that are surrounded by regulatory sequences. A cell’s machinery produces the protein for as long as these instructions persist, and that protein — known as an antigen — stimulates an immune response. By contrast, saRNA jabs go a step further by integrating the genes needed for the replication and synthesis of the antigen-encoding RNA, effectively establishing a biological printing press for fabricating the vaccine inside cells (see ‘Vaccine strategies compared’).

Credit: Nik Spencer/Nature, adapted from “How COVID unlocked the power of RNA vaccines”

In the case of ARCT-154, the antigen is a surface protein called spike that is expressed by SARS-CoV-2. The replication machinery is taken from a naturally occurring virus, a mosquito-borne pathogen known as Venezuelan equine encephalitis virus that causes deadly brain swelling in horses and humans. Notably, scientists at Arcturus have removed key genes from the viral sequence backbone, thus rendering the system non-infectious and safe for use in humans.

People often think that the saRNA vaccine platform is simply a variation on conventional mRNA shots, “but in practice it’s really not”, says Anna Blakney, a bioengineer who studies the technology at the University of British Columbia in Vancouver, Canada. “saRNA is a totally different beast.”

Because of its virus-like nature, saRNA interacts with the immune system in distinctive ways that could prove beneficial across a range of disease scenarios. When it comes to preventing infections, for instance, its self-amplifying capabilities could enable the use of lower vaccine doses.

ARCT-154 requires one-tenth to one-sixth as much vaccine per person as other RNA-based COVID-19 booster jabs. Reducing the amount of vaccine administered in each injection should result in lower production costs. And although the side-effect profile of ARCT-154 seems comparable to that of a conventional mRNA shot1, it is conceivable that the benefits of the platform’s smaller doses will help to mitigate the severity of aches, fevers, chills and other loathsome symptoms collectively known as reactogenicity.

These unpleasant reactions remain a considerable impediment for people to take mRNA-based vaccines. Consider the seasonal influenza vaccine. Existing jabs that use older vaccine technology cause only mild reactions. At present, several conventional mRNA-based flu jabs are progressing through clinical trials and these are showing promising signs of eliciting more protective antibodies than existing shots. Yet their side-effect profiles still leave room for improvement, notes Christian Mandl, co-founder and chief scientific officer of Tiba Biotech in Cambridge, Massachusetts. The saRNA vaccines’ “lower dose could help to solve some of the reactogenicity issues”, he says.

Big shot​

The saRNA vaccine platform does have some downsides. Because of the added genetic instructions, the jabs tend to contain longer sequences — typically at least three times the length of what is used in conventional mRNA shots — which adds complexity to the manufacturing process.

They also engage with the immune system in intricate ways — for example, by forming replication intermediates that help to stimulate beneficial immune-signaling pathways. However, excessive stimulation can backfire, including when the vaccine prompts the immune system to block RNA replication, thereby nullifying its benefits.

It is a delicate needle to thread, says Niek Sanders, a gene-therapy researcher at Ghent University in Belgium and a scientific founder of Ziphius Vaccines, a company in Merelbeke, Belgium, that develops saRNA-based medicines. “You have to find the optimal dose of the self-amplifying RNA in combination with the right delivery system.”

The biotech industry has tried for decades to get the balance right. From 2003 to 2010, for instance, a company called AlphaVax, based in Research Triangle Park, North Carolina, conducted trials of saRNA vaccine candidates for a range of infectious diseases and cancers. AlphaVax ultimately wound down for “business reasons” after failing to secure further investment, says the firm’s co-founder Jonathan Smith, who continues to develop saRNA vaccines as the chief scientific officer of VLP Therapeutics in Gaithersburg, Maryland.

The fruits of fortitude​

With approval for ARCT-154 secured in Japan, its developers are now seeking authorization in Europe; a regulatory decision is expected next year.

“This will hopefully begin to put a nail in the coffin of the idea that self-amplifying RNA is not a viable platform,” says Corey Casper, president and chief executive of the Access to Advanced Health Institute in Seattle, Washington. (Another saRNA jab for COVID-19 was approved on an emergency-use basis in India last year; however, that vaccine’s less-impressive clinical data, the provisional nature of the product’s authorization, and India’s less stringent regulatory requirements have all led industry insiders to consider ARCT-154’s approval to be the field’s true watershed moment.)

More than a dozen saRNA vaccine candidates are currently in clinical trials for a range of applications — from shots for shingles and the flu to therapeutic vaccines for cancer. But researchers are already considering the platform’s broader applications.

For example, the technology might one day be used to produce therapeutic proteins inside the body, says Mark Grinstaff, a biochemist at Boston University in Massachusetts and a co-founder of Keylicon Biosciences in Brookline, Massachusetts.

Manufacturing plants currently use bioreactors to produce such proteins, which are then injected into people who need the treatment. Over the past few months, two independent groups — one involving Smith’s team at VLP Therapeutics, the other involving Grinstaff and his colleagues at Boston University — have posted preprints that describe how altering the chemical backbone of saRNA can diminish the technology’s immune-triggering effects in a positive way. Similar chemical tweaks are commonly used in conventional mRNA vaccines, but not in ARCT-154 or most other saRNA products.

“People are working pretty hard” to expand the platform’s scope, says Smith. “There are some inherent advantages of saRNA — if we’re smart enough to take advantage of them.”

https://www.nature.com/articles/d41586-023-03859-w (Archive)

 

[Agamemnon Busmalis]

It IS coercion. But you can still choose whether or not to comply. A Lotta folks left their military jobs over this. Now, the military is crawling back to these people.

Just goes to show, what you're willing to give up in the short term means you stand to gain more in the long term.

A lot? It was only a miniscule fraction of military personnel that chose to be discharged. 8,000 out of 1,400,000, pretty much all (if not all) of whom were young and single with low rank and limited years of service.

And on top of it, they were screwed for doing so because they received a "general discharge", which significantly limits your post-service benefits and has negative consequences when trying to find civilian employment.

How do you do this if you needed your current job's health insurance for a family member's health issues? Or if you're close to retirement but leaving now would cost you your pension? They did it this way because they knew almost nobody would have the ability to get around it.

So you've never changed jobs in your career before? Most of my job changes have been a trade up in money. But if forced to get a new one right now I could probably find about the same money or maybe just a little bit less.

How are you going to do this when you're competing against the other 84.2 million people employed at jobs with the OSHA mandate? Even if every single open position in the US was with an employer exempt from the mandate, you'd still have 78 million workers unemployed. Small businesses can't just expand payroll on a whim, and if they expanded too much they'd wind up subject to the mandate anyways!

All of this was by design to prevent people from getting around these mandates by the methods you're proposing. And it was only a matter of time if this was upheld that it'd be extended to all employers. Then what would you do?

Wait, are you under the delusion that all healthcare workers in the country were mandated to get the jab? Because my red state is not unique in never mandating that for anyone, much less healthcare workers.

Yes, they were mandated. If your practice didn't comply, CMS cut off your reimbursements for Medicaid and Medicare claims which basically means you go out of business. It is very uncommon outside of a few niche practice areas to not depend on these reimbursements for operations, especially for hospitals and nursing facilities.

 

[Male Idiot]

It is thrme Japanese. The Nip Jab will just give you autism, a cat tail and cat ears. And make your penis 2 inch long.

 

[Cheeseknife]

Yeah no, I'm going to say piss off.

Good attitude. Shame it's directed at me who is just shitposting and not the actual people who mean you harm.

 

[440088]

So you've never changed jobs in your career before? Most of my job changes have been a trade up in money. But if forced to get a new one right now I could probably find about the same money or maybe just a little bit less.

Wait, are you under the delusion that all healthcare workers in the country were mandated to get the jab? Because my red state is not unique in never mandating that for anyone, much less healthcare workers.

So you are afraid of finding a new job (impossible!), were unwilling to move (flyover states brah, not even once!), or are just insane. Probably all 3.

For the sake of this thread, I hereby declare that this man was indeed forced to get the jab, and all pity points should be awarded post haste.

You’re retarded and obviously don’t know what you’re talking about. Yes, all healthcare workers are required to get the jab - or alternately - file for exemption- which may or may not be approved. It’s all states.

You’re clearly talking out of your ass about shit you know nothing about. And have been since the start of this conversation.

it’s very obvious you’re just bullshitting at this point and are unemployed, or employed at some bullshit job like McDonald’s or something equally awful where workers are easily replaceable.

I don’t know why you’re shilling for the jab so much. But it’s bullshit like this is why god awful mandates get passed through.

 

[Cheeseknife]

A lot? It was only a miniscule fraction of military personnel that chose to be discharged. 8,000 out of 1,400,000, pretty much all (if not all) of whom were young and single with low rank and limited years of service.

And on top of it, they were screwed for doing so because they received a "general discharge", which significantly limits your post-service benefits and has negative consequences when trying to find civilian employment.

How do you do this if you needed your current job's health insurance for a family member's health issues? Or if you're close to retirement but leaving now would cost you your pension? They did it this way because they knew almost nobody would have the ability to get around it.

I guess standing up for what you believe in, even when it costs you everything, is actually hard to do.

it’s very obvious you’re just bullshitting at this point and are unemployed, or employed at some bullshit job like McDonald’s or something equally awful where workers are easily replaceable.

Very elitist attitude there. I really want you on my side when the house of cards comes crashing.

 

[JustTheFaxcts]

it’s very obvious you’re just bullshitting at this point and are unemployed, or employed at some bullshit job like McDonald’s or something equally awful where workers are easily replaceable.

Yes, everyone who stood up for their principles works at McDonalds. That's a well reasoned not MATI argument. You're a pussy too terrified of not having someone else supply you with income for even a short while. If you're supporting others and don't have any sort of backup funds or plan B scenario that's entirely on you.

You know what you call someone who will let their body be violated for money? Just admit you're a whore who will prioritize money and comfort while letting others have their way with you.

 

[GunCar Gary]

Yeah bro the government mandates you got to take these experimental shots. Just drop your degree and career and chuck boxes at Walmart. Easy. It’s really your fault you took the shot to be able to keep a livable wage, your degree, your career, and all that bullshit. It’s not technically forced. I mean it doesn’t sound a little….. I don’t know. Like you may have been heavily persuaded. Should have just left homie.

covid was a hard time and i give a lot of leeway to people with families that had to make hard choices about the clot shot. unless you were already rich or a single, lonely loser there were a lot of complicated decisions to make during that time

the real question is: now that the fog of war has lifted from 2020/mid-2021, what are you doing different in your life to protect yourself from being strong-armed by the government again? are you acquiring land? are you searching for jobs, either in new locations or new trades, that are less likely to be affected by government meddling? are you developing skills and buying tools that allow you to be more independent from society in general?

if you have a fully developed brain capable of pattern recognition you should have learned from this experience and should be working hard to make sure you can't be forced to hurt yourself by the government again

if you went through 2020/2021 seeing firsthand the horrors of what the medical system was doing and are just trying to shrug off the last few years and go back to normal in bughiver hell then you're an idiot. no sympathy

 

[LurkTrawl]

You're a pussy too terrified of not having someone else supply you with income for even a short while. If you're supporting others and don't have any sort of backup funds or plan B scenario that's entirely on you.

I'd say that they're a victim of abhorrent violations of basic human rights conducted by the government and the institutions under it but hey you do you.

 

[JustTheFaxcts]

I'd say that they're a victim of abhorrent violations of basic human rights conducted by the government and the institutions under it but hey you do you.

Which they only get away with because of cucks who will sell themselves for money.

 

[440088]

covid was a hard time and i give a lot of leeway to people with families that had to make hard choices about the clot shot. unless you were already rich or a single, lonely loser there were a lot of complicated decisions to make during that time

the real question is: now that the fog of war has lifted from 2020/mid-2021, what are you doing different in your life to protect yourself from being strong-armed by the government again? are you acquiring land? are you searching for jobs, either in new locations or new trades, that are less likely to be affected by government meddling? are you developing skills and buying tools that allow you to be more independent from society in general?

if you have a fully developed brain capable of pattern recognition you should have learned from this experience and should be working hard to make sure you can't be forced to hurt yourself by the government again

if you went through 2020/2021 seeing firsthand the horrors of what the medical system was doing and are just trying to shrug off the last few years and go back to normal in bughiver hell then you're an idiot. no sympathy

Did you even read what I wrote, lol.

I said I refused to get any of these boosters and whatever other shit.

This original vaccine bullshit was when it first went down. I’ve not gotten any boosters or anything since then. And refuse too. But I - and most people - were blinded sided by the first original mandates.

And I never asked for your sympathy. Also stop larping as some fucking dude that’s going to go live in a cabin alone in the woods or whatever. Cause we both know you aren’t that guy. I’ve taken steps to protect myself from bullshit mandates. And it’s actual protection. Not whatever the hell you’re on about.

 

[Agamemnon Busmalis]

I guess standing up for what you believe in, even when it costs you everything, is actually hard to do.

Sometimes you just can't. What would you do if you had a sick or elderly family member and you needed your health insurance for their medical care? You can't go to the ER for chemotherapy or surgery. There physically weren't enough jobs to employ all of the people impacted by this mandate even if they wanted to leave.

The other piece of this is how quickly it was implemented. The regulations were issued in November 2021 and effective in early January 2022. That means you had barely two months, if that, to come up with a solution. Companies aren't going to hire highly qualified people to work in low-skill or unqualified positions, so that doesn't really work as an option, and you can't go into the trades without an education in the field. Most factory work is at employers subject to the mandate, same with trucking.

All of this was designed to make it as difficult as possible for people to get around it. And like I mentioned before, what would you do if it was extended to ALL employers?

 

[LurkTrawl]

Which they only get away with because of cucks who will sell themselves for money.

I'm not going to say that there isn't a nugget of truth to that.

What I will point out is that people who blame the victims of such policies are doing the government's work for them, by blaming their victims instead of the government to begin with. As well as being unreasonable, uncaring shit-dicks about it which makes it difficult for people who were victimized to want to side with people who are against such measures who had the luxury of making that choice.

 

[JustTheFaxcts]

What I will point out is that people who blame the victims of such policies are doing the government's work for them, by blaming their victims instead of the government to begin with. As well as being unreasonable, uncaring shit-dicks about it which makes it difficult for people who were victimized to want to side with people who are against such measures.

Fair enough, it's just frustrating to see. One way we've gotten to this point is people not taking personal responsibility and relying on institutions. Also being unwilling to suffer any disruption to their life to uphold a moral stance. The writing was on the wall way before COVID, although it was hopefully a huge wake-up call for many.

Also, compromising on fundamental moral principles for money should be a huge eye-opener for someone like @440088. The fact that he can't admit it was a choice he made, regardless of the complexities of life, shows incredible weakness of character.

 

[GunCar Gary]

But I - and most people - were blinded sided by the first original mandates.

it wasn't a surprise at all if you had been paying attention to how covid was being handled by governments and hospitals. even if this is something you had trouble recognizing in 2021 it's something that should be obvious now when you've had time to reflect on how authoritarian and anti-science virtually all laws and protocols related to covid were

Also stop larping as some fucking dude that’s going to go live in a cabin alone in the woods or whatever.

there are plenty of changes you can make in your life to become more independent that aren't being a crazy mountain man. moving away from bughives != living in the middle of nowhere with no power or running water

you keep deflecting on obvious mistakes you've made which makes it seem like you're just going to keep repeating them. it seems every day this whistleblower's words become more true: it's a dangerous place -- i would not take a family member to a hospital

 

[Drain Todger]

Self replicating mRNA is just called a fucking virus, jesus christ. I want off. Please Mr. Bones.. Please....

They literally took the replicase gene out of a virus and reused it.

The replication machinery is taken from a naturally occurring virus, a mosquito-borne pathogen known as Venezuelan equine encephalitis virus that causes deadly brain swelling in horses and humans. Notably, scientists at Arcturus have removed key genes from the viral sequence backbone, thus rendering the system non-infectious and safe for use in humans.

Regular RNA polymerases in cell nuclei make RNA from DNA. Replicase, or RNA-dependent RNA polymerase, makes RNA using RNA as a template.

RdRps are known to have a very high error rate.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850383/

RNA genomes dominate the world of viruses. Their success results from the possibility of accommodating rapid changes via mutations, which aids in countering constant challenges imposed by the host physiology [1]. Of the many factors that substantiate the role of RNA dependent RNA polymerases (RdRps) in viral evolution, the primary one concerns high rate of error during the copying (≈10−4) process due to the lack of a proofreading exonuclease activity [1]. The increased rates of mutation in the progeny viral population allows some of the variants to be selected under the pressures imposed by the host defense mechanisms and other environmental factors [2]. In addition, the process of strand switching by RdRps during replication allows for recombination that facilitates rearrangement of genes or acquisition of new ones from other viruses or hosts [3].

Without high-quality proofreading of the amplified RNA, there's no way to know the purity of the proteins that will eventually be produced from it. They could be a large portion gobbledigook.

Isn't it weird how the past few years have normalized injecting mystery gene therapy human-cell-as-bioreactor bullshit into people without doing decade-long meticulous human trials?

 

[Ebonic Tutor]

Good attitude. Shame it's directed at me who is just shitposting and not the actual people who mean you harm.

You're not shit-posting you're a gaslighting faggot making excuses for the medical industrial complex / govt pushing this ridiculous shit on people who's livelyhoods were in danger due to basically nowhere hiring during the shit.

Fuck off with that "well you can always get another job" shit, you retarded ass nigger that belongs on reddit with that wonderful fucking logic you have.

 

[Cheeseknife]

Sometimes you just can't.

You can. It just requires a backbone. Anyone telling me otherwise might as well be justifying their government essentially earmarking their cattle.

 

[Cheeseknife]

You're not shit-posting you're a gaslighting faggot making excuses for the medical industrial complex / govt pushing this ridiculous shit on people who's livelyhoods were in danger due to basically nowhere hiring during the shit.

Dude, you're the one making excuses for it. Don't need to gaslight you when you're already drinking the Kool-aid.

 

[Agamemnon Busmalis]

You can. It just requires a backbone. Anyone telling me otherwise might as well be justifying their government essentially earmarking their cattle.

How are you going to address those issues I raised, like affording medical care for a sick family member? You can't just get on Medicaid immediately (if you are eligible at all) and you can't go to the ER for surgery or chemotherapy. What do you do if the hospital requires vaccination like St. Jude did?

If you lose your house, where are you going to live? Being homeless is a lot worse for your health and life expectancy than any COVID shot.

 

[Ebonic Tutor]

How are you going to address those issues I raised, like affording medical care for a sick family member? You can't just get on Medicaid immediately (if you are eligible at all) and you can't go to the ER for surgery or chemotherapy. What do you do if the hospital requires vaccination like St. Jude did?

If you lose your house, where are you going to live? Being homeless is a lot worse for your health and life expectancy than any COVID shot.

This is some nigga w/ a shit-tier job (or no job) that thinks all this shit is so easy to stand up against.

He's the same type of faggot that blames Trump for the J6 people being in prison when he couldn't even legally do anything about it, it's all gay ops headgames shit to them.

Dude, you're the one making excuses for it. Don't need to gaslight you when you're already drinking the Kool-aid.

Says the one that makes claims then pulls the "I was only pretending to be retarded"

No you're somebody that's never actually had to struggle so you think it's fucking way easier than it actually is to do what you were saying. Idiots that aren't retarded faggots pushing an agenda remember exactly how it was back then and you're not going to fool them with the, "well you should have still quit your job that supported you and your family, there were other jobs available!" You know that's bullshit and I can tell you're a retarded child that never had to work to support anybody at best or a lying dishonest fuckwit shill at worst.