Having been subjected to needles routinely from the time I was a tyke, I developed a pathological hatred to being injected.  After all, it would not be atypical for me to have been subjected to 150 injections in any given year, until I turned 12.

Now, you do notice I didn’t say I didn’t get those inoculations.  Oh, sure, I ceased the allergy shots since all I got for my thrice weekly shot was a swollen arm. Those jabs never stopped me from having a breathing episode, so why would I keep getting zapped.  But, for diseases- or even to prevent the dreaded tetanus reaction- I just closed my eyes and waited to get those pinches in my arms.

But, now, giving our upper arms to the nurse or doctor may become a thing of the past.  After all, if folks can successfully encapsulate RNA and/or DNA in a microsphere, there’s no reason those capsules must be injected in our arms.

Which brings up another development by the most prolific Bob Langer, along with his frequent research companion, Giovanni Traverso.  I’ve told you about Bob many times, but the last time I shared information about both Giovanni and Bob was in 2017.  Both of these PhD’s are associated with MIT and Brigham and Women’s Hospital, among other affiliations.

And, now, it seems that they have contrived a process to deliver nucleic acid drugs (think mRNA vaccines and antisense oligonucleotides) to our bodies via the oral route.  The impediment to such deliveries has been the harsh conditions in the digestive tract, which would normally degrade and/or destroy the materials.

But, for this effort, Drs. Langer and Traverso built a study team that included a slew of folks also from the Chem E Department of MIT (Drs. Alex Abramson, Ameya R. Kirtane, Yunhua Shi, Grace Zhong, Joy E. Collins,  Siddartha Tamang, Keiko Ishida, Alison Hayward, Jacob Wainer, Netra Unni Rajesh, Xiaoya Lu, Yuan Gao,  Paramesh Karandikar, Chaoyang Tang,  Aaron Lopes, and Aniket Wahane; plus Drs. Morten Revsgaard Frederiksen and Brian Jensen  of Novo Nordisk; as well as Dr. Daniel Reker of the Koch Institute of MIT).  Their article, Oral mRNA delivery using capsule-mediated gastrointestinal tissue injections, was recently published in Cell.

The team was able to deliver 150 mg of RNA to a pig’s stomach.  That doesn’t sound like much- until you realize that another of Langer’s concepts employs 100 mg of mRNA (the Moderna Vaccine).  Oh, and the Pfizer/BioNTech uses all of 30 mg of mRNA in their inoculation.

This is not the first capsule delivery the team has developed.  Nope- they’ve found it possible to deliver monoclonal antibodies (which are relatively large molecules) and insulin into stomach linings.

This development employed poly (β amino ester) mRNA nanoparticles for transfection efficiency.   The branched version of these polymers were more effective than the linear versions; moreover, they were more likely to be able to enter the target cells.

First, the team started by injecting the mRNA nanoparticles into mice stomachs, which enabled them to demonstrate that the concoction was easily incorporated by the cells.  (The protein was expressed in both the stomach and liver of the mice; clearly the cells had sufficient uptake, since the presence of the material in the liver meant they were transported there to effect metabolic detoxification.)

The next step required the freeze-drying of the complexes; that’s why Novo Nordisk was involved.  (Part of that firm’s specialty is freeze drying of biomaterials.)  The end result was 50 mg capsules, which necessitated the use of three of them to deliver the 150 mg of mRNA.  The pig studies demonstrated that the drug did make it to the cells of the stomach- but not its other organs.

The question now is if the immune response will be large enough if the drug is just delivered to the cells of the stomach.  Or, what other dose will be necessary to trigger the desired immune response.

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