Glueing wounds back together, human cloning, and using bio-nano to infiltrate synthetic DNA.

02 May 2014

If you've ever been injured enough to need stitches, you know that it's no picnic. Administration of local anesthetic aside (which usually involves multiple shallow injections directly into the wound site), flesh is touchy stuff to suture back together. Get the suture too close to the edge of the wound and it might rip through and pop open again. There may not be enough usable skin far enough away from wound site to stick a needle through (such as on particularly skinny fingers or the backs of some ankles). Some parts of the body just don't take well to being sewn up because they're too soft, like the liver or the spleen. Kind of icky, when you think about it. A French research team published a paper in the journal Angewandte Chemie about a novel technique for wound closure that involves neither needle nor thread, but a solution of nanometer-scale particles of iron oxide and silicon dioxide in an aqueous solution sprayed directly into the wound, which is then pinched together for about a minute. Other surgical adhesives have been used over the years with varying degrees of effectiveness (makers have no doubt tried using superglue to patch up minor injuries (and alerted neighbors for blocks around)) but adhesives also have varying degrees of toxicity within the body; additionally, they don't always work under suboptimal (read: inside the body and mixed with body fluids) conditions. The principle is similar but counterintuitive in a biotech context: The nanoparticles are attracted to the membranes of the cells that comprise the surfaces of the open wound. They also probably bind to one another strongly due to their immensely small size (billionths of a meter) which would bridge any gaps between surfaces. This seems to help the surfaces of the wound stick to each other, holding the wound closed to facilitate the healing process. The nanoparticles are small enough that they don't seem to impede the regeneration of tissue any, unlike a layer of surgical adhesive or the materials that some sutures are made of.

In other bioengineering news that is certain to make the blood pressure of some go stratospheric, human cloning has taken a step forwards. Through a process called somatic cell nuclear transfer, in which the nucleus of a cell is extracted under a microscope using microsurgical techniques and inserted into an unfertilized egg cell, cells from a 35 and a 75 year old human were successfully cloned and caused to develop into early stage embryos. Those cloned early stage embryos were then used to derive pluripotent stem cells that were genetically identical to the donors. The cultured stem cells were induced to differentiate into several different kinds of mature cells in vitro, including cardiomyocytes, or heart muscle cells. This represents a breakthrough because under most circumstances it's very difficult to get nucleii from adult human cells to do this sort of thing; it seems comparatively easier to induce adult cells to de-differentiate back into pluripotent stem cells and then re-differentiate than it is to get an adult nucleus to function properly within an egg cell. The cloned embryos would probably not have been able to develop into sci-fi perfect clones of the donors if they were incubated under optimal conditions for reason I don't pretend to understand, but I hypothesize that the phenomenons of epigenetics and telomere shortening due to the aging process are implicated (to some extent, anyway). Cloned complex animals (like Dolly the sheep) take many, many attempts and fiddly alterations to the process just to get going, and there are invariably many failed attempts that fail to grow properly. Clone masters we are not. Not yet, anyway. Along those lines, another procedure arguably just as difficult to accomplish as cloning is modifying the inner workings of a living cell and keeping it, well, living. After all, viruses do it every day so how hard could it possibly be?

Heh heh heh.

Scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University published a paper in the journal ACS Nano describing the results of a recent experiment in which they built nanoscale devices functionally similar to viruses capable of infiltrating living cells (mouse cells in this case), potentially to install arbitrary strands of DNA. They're not quite at the point of building completely synthetic viruses with a specificity equalling viruses you'll find in nature but this is an impressive achievement indeed. The research team used a technique called DNA origami to fold strands of synthetic DNA into three dimensional shapes that were then enveloped with double layers of phospholipids, biological polymers that closely mimic the chemical structures of cell membranes. The DNA (folded in a tetrahedral shape and apparently acting as a chassis) was engineered to have attachment points for the phospholipid molecules to grab onto and arrange themselves into an appropriate shape. A bio-neutral UV reactive dye was added to the synthetic nanoviruses as well to act as a sensing marker. As far as the immune systems of the lab mice were concerned the synthetic nanoviruses coded as mouse cells (albeit probably strange ones) and sailed right past undetected. By shining UV light on the mice infected with the nanovirus they were able to determine whether or not the inoculation took and if so how far it progressed. The whole bodies of the lab mice glowed for hours, meaning that the nanovirus inoculation hit just about every visible part of each lab mouse (and at least some of their insides, if examination of their bladders is any indication).

Where could this lead? For starters, synthetic viruses designed to seek out specific kinds of cells in the body (like neurons or the islets of Langerhans in the pancreas) for the purpose of gene therapy using engineered DNA sequences to patch genetic defects in vivo. I also imagine scenarios in which they'd come in handy for germline engineering, in which modifying the handful of cells that comprise early stage embryos would be comparatively simpler, and the genetic modifications would then carry over into the rest of the organism's cellular makeup as the cells replicate and differentiate into aspects of the whole organism. All in all, I think this is definitely a technology to keep a sensor net trained on because it has too many potential applications in the future.