A Shabby Pop-Sci Article on the Minicircle Trial of Follistatin Gene Therapy

Minicircle is working towards the upregulation of follistatin, an inhibitor of myostatin and thus an interesting target for improved muscle growth and treatment of sarcopenia. Follistatin and myostatin are well studied genes in this context, and there are any number of animal studies, as well as human trials of various approaches to myostatin inhibition. As I have long said, follistatin and myostatin are probably the most compelling, least risky genes to start working on if interested in gene therapy development. There is a great deal of animal and human data to support this work.

It is always annoying to see shabbily written popular science articles in which ignorance is brandished with a sort of pride. The author of today's article couldn't get Minicircle to comment on the details of their work, has no real idea as to what is going on under the hood, and so forges ahead with a mix of snark and commentary from various people who also don't know what Minicircle is doing, or the nature of their gene therapy approach.

I am a participant in the Minicircle follistatin trial. I've also signed a non-disclosure agreement, so don't ask me for details. The company has an interesting, novel technology for the delivery of gene therapies, and is undertaking a responsible, low-cost, first-in-human clinical trial outside the US with educated volunteer participants from the self-experimentation community. It consistently amazes me, the degree to which hostility is poured upon those who choose not to engage with the journalistic and regulatory priesthoods in exactly the approved fashion.

The present system of regulation, and the enormous costs it imposes on development and discovery, must change. We live in an era in which a prototype gene therapy can be safely assembled for a few thousand dollars in cost of goods. It cannot continue to be the case that development only progresses at a cost of tens of millions of dollars to reach initial human trials, and hundreds of millions to billions of dollars to allow the average person to be permitted to use a treatment.

This biohacking company is using a crypto city to test controversial gene therapies

Over the past few years, a parade of newly released gene therapies have consecutively claimed the title of most expensive drug in the world; the current honor goes to the $3.5 million hemophilia B treatment Hemgenix, launched in November 2022. Minicircle is taking something of a different tack. The startup, which is registered in Delaware, aims to fuse elements of the traditional drug testing path with the ethos of "biohackers" - medical mavericks who proudly dabble in self-experimentation and have long hailed the promise of DIY gene therapies

The eccentricities don't end there. Minicircle's trials are going ahead in Próspera, an aspiring libertarian paradise born from controversial legislation that has allowed international businesses to carve off bits of Honduras and establish their own micronations. It's a radical experiment that is allowing a private company to take on the role of the state. While much attention has been paid to the charter city's use of Bitcoin as legal tender, the partnership with Minicircle is an important milestone toward another goal - becoming a hotbed of medical innovation and a future hub of medical tourism.

It's against this unusual backdrop that Minicircle is trying to lead biohacking's charge into the mainstream, or at least somewhere near it-studying gene therapies that target familiar conditions like muscular disorders, HIV, low testosterone, and obesity, and doing so with the backing of tech moguls and under the purview of bespoke "innovation-friendly" regulation. It ultimately aims to democratize access to gene therapies, with an emphasis on discovering the right nucleic cocktail to promote longevity. 

Most scientists I spoke with are less than enthusiastic about Minicircle's undertaking, expressing skepticism about its methods and aims, while experts in medical ethics are concerned about how the trials will move forward - and what they could mean for the burgeoning and sometimes unscrupulous medical tourism industry.  These experts also say the red-tape-trimming stance of special economic zones like Próspera can set off alarm bells (though the charter city staunchly defends its regulations).

At least one prominent scientist sees a potential upside to growth in the biohacking space: George Church, a professor of genetics at Harvard Medical School who has previously consulted on biohacking endeavors, tells me he welcomes the evolution of biohacking self-experimentation into full-blown clinical trials. He isn't familiar with Minicircle's work specifically, but he says of the general premise, "As long as nothing goes wrong, it could herald a revolution in cost reduction." That, of course, is a big caveat. 


Scathing? Yes.

But they're watching.... They're talking about it...

Posted by: Gregory Schulte at February 14th, 2023 5:39 PM

Screw MIT Technology Review and the medical establishment. Given how they grossly violated informed consent in coercing people to undergo medical treatment with so-called "vaccines" that are injuring and killing as many people as the original virus did, the medical establishment and bioethics people gave up having any say in how people go about their personal medical business. The entire academic and medical establishment in the U.S. deserves to be hanged for what they have done over the past three years. We need a Nuremberg II war crimes trials for what they did.

Posted by: Abelard Lindsey at February 15th, 2023 9:21 AM

I wonder what vector they are using? AAV? If they can achieve reasonable expression levels their mini plasmid for a broadly neutralising antibody against HIV would be very useful.

This technology could be useful in producing catalysing antibodies against amyloids.

I really hope this does work out as the FDA has gotten to a ridiculously suffocating level.

Posted by: jim at February 15th, 2023 2:18 PM

As minicircles may achieve longer expression times than mRNA, they may be a better candidate for the cosmetic production of collagen in the skin than the mRNA that was tried in that recent study in mice with extra cellular vesicles (although I remember the loading of the EVs was performed with a device that might not work well with mini plasmids).

Also as minicircles are DNA and not mRNA, they could be room temperature stable which means someone could theoretically set up a mail order business on Próspera in Honduras sending cosmetic micro needle patches to more restrictive countries.

Posted by: jim at February 15th, 2023 4:40 PM

Hello Reason, will you, at least, say at the end of the trial, how do you feel with the therapy? If you feel stronger or your muscle mass has increased?

Posted by: Josep at February 16th, 2023 4:57 AM

Another thought is that they could use minicircles to produce an antibody to myostatin as well as producing follistatin for an increased effect perhaps?

The ability to use gene therapy to get the body to produce antibodies to targets that are usually hard to vaccinate against such as HIV or Stpahylococcus auerus antigens would be hugely valuable. A definite advantage of gene therapy antibodies over antibodies produced by standard protein administration vaccination would be the absence of a T cell response to the protein. This really could revolutionise the use of biologics (basically antibodies at this time) in medicine as they wouldn't have to be grown expensively in vats and the injected weekly or fortnightly.

Posted by: jim at February 16th, 2023 2:47 PM

Reason, could you share how I join the trial pls? Many thanks

Posted by: Joe Da Silva at February 18th, 2023 5:46 PM

@Joe Da Silva: I don't know if there are spaces left, but reach out to Minicircle directly and ask.


Posted by: Reason at February 18th, 2023 6:39 PM

Reason - rhetorical . . . . and applying to other actors, not just you . . . . how can the effects, including current and leftover substances of current and leftover bio-hacking, self-experimentation be properly reconciled while testing a novel substance in a clinical phase trial?

Posted by: Jeff at February 19th, 2023 11:50 PM

Plasmids have been used to create anti-venom, insulin, and other critical medicines for decades. Putting them in a human body and giving them a transfection agent and transcription kill switch is one of the more elegant areas of microbiology I've seen. Call it "bio hacking" all you want, it's just amazing and potential to transform the lives of the sickly and elderly.

Sounds like the "journalist" read the word 'libertarian' and abandoned any intent to fairly cover Prospera or any of its potentially innovative companies.

They write about how other "experts say" that follistatin wouldn't be a target for the fountain of youth, as if the product being researched is advertised as such. Some real "journalism" there!

Another great example of "journalism" is the author's absolute in-your-face (intentional) hypocrisy of denigrating companies which collect data offshore and then return stateside to get the funding for stateside studies……and then immediately comment about how it is a common practice that many (successful) biotech researchers have done.

I guess these people are just stubborn but who cares. Science moves forward with or without your subscription to its realities

Posted by: Alec Spier at February 21st, 2023 1:30 PM

Just seeing this. Thanks

Posted by: Ron Primas at September 17th, 2023 11:28 AM

Hi Reason, any updates on the results you can share?

Posted by: Joe Da Silva at November 23rd, 2023 4:11 PM

Unfortunately I can't share my results publicly, at least not until Minicircle have published the trial results.

Posted by: Reason at November 23rd, 2023 4:41 PM

What is a good starting place to read about the FDA and regulations around this, from a somewhat libertarian position, but not overly prejudiced?

Posted by: JP at January 5th, 2024 2:21 PM
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