Genetic Engineering Will Make Pills and Needles Obsolete (and Enable Radical Life-Extension)

11-Jul-2017

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Dear Reader,

Most medicines, up to this point, have been delivered into the body via simple pills or needles. But now, new drug delivery systems enabled by genetic engineering will make these old systems obsolete.

Our genomes are the chemical factories of our bodies. They produce everything that we are. This means that genetically engineered cells can use our genomic machinery to make valuable bioactive molecules. There are two major ways to do this.

One uses stem cells that are designed to become certain types of adult cells. For example, hemophiliacs could have cells that make Factor XI implanted into their bodies. This would enable normal coagulation. This approach could also be used to treat those who are deficient in other compounds. This includes diabetes, atherosclerosis, age-related muscle loss, and obesity.

The second cell-engineering strategy uses engineered gene plasmids. Plasmids are microscopic circular rings of DNA like those found in our mitochondria and bacteria. Almost any gene can be inserted by genetic engineers into these rings. Once activated, the transcriptional process runs nonstop to make the needed molecules… just like a model train on a circular track.

While this may seem like science fiction, this approach is already widely used in agricultural animals. FDA approval for human use is a little way off, but that might change due to the Zika virus threat.

Inovio’s Zika Vaccine

Mosquitos infected with the Zika virus are moving northward from Central America. Infections have recently been reported in Mexico. Because Zika can also be spread through contact, the CDC recommends that travelers use condoms or not have sex while there.

Inovio (*see disclosure below) was the first company given FDA permission to begin clinical trials of a Zika vaccine. In animals, the company’s GLS-5700 DNA vaccine protected against Zika-related brain damage. Uninfected humans given the vaccine generated a similar immune response to the Zika virus.

In the case of the Zika vaccine, Inovio’s plasmids produce antigens that create immunity to the disease. Similar strategies are being developed for cancers.

Because Inovio’s plasmids create molecules that lead to immunities, they’re called vaccines. But the term grossly oversimplifies the platform. I prefer to think of these plasmids as DNA-manufacturing plants.

Inovio’s secret sauce, by the way, is electroporation. Tiny openings in cell membranes are temporarily opened to allow plasmid entry using precise electrical signals.

My real interest in this technology, though, goes beyond fighting viruses and cancers. DNA plasmids are microscopic drug stores. They are able to constantly create and deliver life-saving and life-extending drugs. That means many drugs (like costly monoclonal antibodies) could be produced within patients’ bodies.

In the future, an injection of plasmids every year or two could replace routine pills and injections. Because the plasmids create the drugs, the middle-man is cut out of the process… along with high drug costs.

DNA Plasmids and Anti-Aging Medicine

This drug delivery strategy is of great interest to those in the field of geroprotection or anti-aging medicine. Though our regulatory system is lagging, scientists now know that it is often easier and cheaper to prevent diseases rather than cure them.

As we age, certain protein and hormone levels start to dwindle. But what if we could return them back to youthful levels? Current candidates include GDF11, KLK1, TIMP, and growth hormone (GH).

Restoring GH levels in those with adult growth hormone deficiency (AGHD) yields apparent benefits. These include improvements in body mass index (fat to muscle ratio), skin tone, and organ health.

When GH research first came out, it was embraced by the anti-aging and athletic communities. Since then, side effects and inconclusive evidence of improvements in longevity have lowered expectations, but it is still widely used.

There is a superior solution. It is growth hormone releasing hormone (GHRH).

The hypothalamic hormone GHRH stimulates natural production of GH. Use of GHRH for the enhancement or restoration of growth has been extensively researched, generating a great deal of scientific and pharmaceutical interest.

Though virtually no adverse events have been linked to GHRH, it is not widely used. The reason is that it is very costly and short acting. With a half-life in the blood stream of only six to seven minutes, GHRH would have to be injected frequently to produce significant benefits.

Inovio solved this problem by creating plasmids that constantly manufacture GHRH within cells. GHRH is then released into the bloodstream where it circulates.

This is not a new technology. GHRH plasmids have been injected into tens of thousands of animals. This includes mice, rats, dogs, pigs, horses, and cattle. GHRH plasmid implants are very safe; their use is approved for agricultural animals in Australia and elsewhere.

Relatively few cells need to be converted to produce GHRH because the hormone impacts GH production at very low levels. And, this endogenously produced GH acts within the body’s regulatory system.

Unlike GH injections, GHRH made within the body causes no spikes in blood levels that can lead to problems. If there is excess GHRH, it is ignored. So GH overdosing is not possible.

Other parts of the regulatory system such as insulin-like factor I (IGF-I) are adjusted by the body to match GH levels. As a result, treated animals show no short- or long-term systemic adverse effects. (These include the side effects linked to growth hormone therapy such as cardiac hypertrophy, insulin resistance, enlarged organs, and oversized body parts.)

Animal studies of plasmid-based GHRH delivery have shown a reversal of cancer-induced anemia and cachexia. Animals with cancers treated by GHRH had better survival rates than untreated animals. They also had better disease rates, acuity, activity level, fertility, immune system function, exercise tolerance, and life span. Benefits from a single treatment were seen for more than a year after treatment.

At this point in the development of plasmid drug delivery, the creation of  for humans would be simple and cheap. An off switch could even be engineered into the treatment. The only real challenge, of course, is regulatory. The same is true for the implantation of engineered stem cells that produce GHRH.

I predict, though, that we’re going to reach some sort of tipping point because the aging crisis will continue to worsen. Then, people will be allowed to make their own medical decisions.

(*Disclosure: The editors or principals of Mauldin Economics have a position in this security. They have no plans to sell their position at this time. There is an ethics policy in place that specifies subscribers must receive advance notice should the editors or principals intend to sell.)

Sincerely,

Patrick Cox
Editor, Transformational Technology Alert

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