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Breakthrough here is the ability to image embryos comprised of living cells as opposed to post-mortem embryos.

original doi: https://doi.org/10.1016/j.cell.2023.06.003

[–] [email protected] 0 points 2 years ago (1 children)

That's fair. I couldn't find much info on their website, so I assumed this was another make insulin cheap using "biohacking" deal. I don't have any experience with small molecule synthesis or dry powder manufacturing, so I can't really speak to how feasible this may be. However, having seen first-hand all the ways simple manufacturing steps can go wrong, the risk of consuming a medication that hasn't been through rigorous QA/QC makes me very wary.

[–] [email protected] 1 points 2 years ago (3 children)

Apologies for the long post. I don't mean this as an attack on OP, just trying to illustrate why actually doing this is a bad idea.

I have seen efforts like this in the past, especially centered around efforts to manufacture insulin cheaply. While I get that medicine cost and availability is broken at a fundamental level in the US, the solution is a political one rather than to run a wildcat bioreactor. There is simply no way to safely manufacture biologics using a 3d printed bioreactor. Let's look at the manufacturing process to get an idea of why.

Staring with the bioreactor, you would need some way to sterilize it before use (not just sanitize, there's a difference). There are plastic bioreactors that are used in industry, but they are large, single-use bags that are sterilized using gamma or x-ray radiation. Most industry bioreactors are made of stainless steel to withstand the harsh treatment required to re-sterilize them (steam or hydrogen peroxide).

Moving down the chain from the bioreactor, you need some way to remove your product from the harvested liquid. This is usually done through lysing the cells you have grown and then running this lysate through a series of chromatography columns of varying types (affinity, ionic, etc.) to systematically remove all the junk left over from your cellular media and the cells you have lysed. Even if you could (unsafely) grow your cells and drug in a 3d printed bioreactor, you don't have these kinds of things at home and can't just get them from Amazon.

However, let's say that you could get past the purification step, what's next? You find yourself with a large volume of very dilute medicine suspended in a chromatography buffer. The next step is what is called UF/DF, or ultra-filtration/dia-filtration. This step, paradoxically done DF first, uses filter membranes and large amounts of buffer and some pressure to first swap out the buffer that your medicine is in to the target formulation that you want to inject and then concentrate it down to a manageable volume. If you are working at small scale, then you can probably replace this step with just one filter and a centrifuge. Remember that while you are doing all this, everything that comes into contact with your drug needs to be sterile (even the air).

I think I have made my point, but for actual drugs there are more steps beyond this. Post-UF/DF is what is referred to as drug substance (DS) in the industry. You still need to go through a sterile fill-finish process to get drug product (DP) that is what is actually given to a patient. If you really want, I can go on another long tirade here since this is the step my job focuses on.

I have worked on these manufacturing processes and seen them fail a lot for very hard to catch problems. Without all the in-process controls and testing we do, there would have been serious risks of giving bad DP to patients. If you have read this far, then I hope I've convinced you not to give this kind of thing a try.

The real problem this is trying to solve is a political one. We should be advocating for better access to medications and reforming how costs are dealt with. It doesn't matter what your political persuasion is, I think everyone agrees healthcare in the US is broken and it's time something is done about it.

 

This summarizes a paper in which researchers created a microscope probe using a single, 110 µm diameter optical fiber. An interesting technique from this that I had not seen before, was that the end of the optical fiber is angled and coated with aluminum to create a mirror looking perpendicular to the length of the fiber. This enables researchers to image living cells less intrusively.

doi: https://dx.doi.org/10.1038/s41467-023-36889-z

 

This article describes using lipid nanoparticles (LNPs) containing silencing RNA (siRNA) to slow or prevent the spread of cancerous multiple myeloma cells through the body.

What I found interesting about this approach is that these LNPs do not target the cancerous cells themselves, but rather targets healthy endothelial cells lining blood vessels in the body. The mechanism of action is to reduce the expression of a protein (CyPA) that cancer cells use to aid their spread through the body. So, these LNPs are simply used to help contain and localize the cancerous growth while traditional cancer treatments are used to treat the malignant cells.

A significant challenge for this approach going forward is tuning the targeting and biodistribution of the LNPs. Most LNP treatments end up in either the liver or spleen where they transfect cells in those organs and express protiens. I don't have direct experience with siRNA molecules, but transfecting epithelial cells in a lasting way could prove difficult as it scales up from mouse models.

doi: https://dx.doi.org/10.1073/pnas.2215711120

 

Getting therapeutics to cross the blood-brain barrier is one of the biggest hurdles to many investigational neuroscience macromolecules. This approach of using a proven mechanism of action (ultrasound) in a device that is easily implantable and does not need to later be removed looks promising.

doi: https://dx.doi.org/10.1126/sciadv.adg6075

 

Some recent evidence points to the Earth's magnetic field playing a part in preferentially selecting right-handed chirality in RNA precursors. This work is not complete though as not every nucleotide can be made from this process yet, but it is so far, the best explanation available as to why genetic material and amino acids are exclusively R and L (respectively) oriented.