Scientists discover enzyme that can change blood types

[Borgholio]

http://www.sciencealert.com/scientists- ... blood-type

Scientists have discovered that a particular type of enzyme can cut away antigens in blood types A and B, to make them more like Type O - considered the 'universal' blood type, because it’s the only type that can be donated to anyone without the risk of provoking a life-threatening immune response.

The team, from the University of British Columbia of Canada, worked with a family of enzymes called 98 glycoside hydrolase, extracted from a strain of Streptococcus pneumoniae. Over many generations, they were able to engineer a super high-powered enzyme strain that can very effectively snip away blood antigens where previous generations of the enzyme struggled. "A major limitation has always been the efficiency of the enzymes," one of the team, Stephen Withers, said in a press release. "Impractically large amounts of enzyme were needed."

Getting the right type of blood when you need it is crucial, and it has to do with the different types of residue that can accumulate the surface of red blood cells. Both blood types A and B have this residue - A has an N-acetylgalactosamine residue, and B has a galactose residue - and Type AB has a mixture of both. Only Blood Type O is free from this residue, which means it can be received by any patient, no matter what type they’re carrying.

Withers and his team managed to create their 'mutant' enzyme strain using a technology called directed evolution, which allows them to insert many different types of mutations into the gene that codes for it, and by progressively selecting strains that are the best at snipping away the blood antigens, were able to create an enzyme that’s 170 times more effective at it than its parent strain. They published their results in the Journal of the American Chemical Society.

"The concept is not new, but until now we needed so much of the enzyme to make it work that it was impractical," said Withers. "Now I’m confident that we can take this a whole lot further."

While the current enzyme strain is not yet capable of removing 100 percent of the antigens from Blood Types A and B, which is where it needs to get if the researchers want to make any real use of it, the team is confident that they’ll get it there so they can try it out in clinical trials. Even the smallest amount of antigen in donated blood can set off a dangerous immune response in the recipient.

"Given our success so far, we are optimistic that this will work," says Withers.

[Broomstick]

Wow - very interesting.

Could this possibly be used to remove antigens from other sorts of tissues, allowing greater ease of organ transplant with less problem of rejection? Way down the line, of course, there would have to be a lot of steps between where we are now and anything like that.

[Borgholio]

Yeah they still have a ways to go before they get even the blood ready, but it's very neat they were able to get as far as they did.

[KroLazuxy_87]

Wow - very interesting.

Could this possibly be used to remove antigens from other sorts of tissues, allowing greater ease of organ transplant with less problem of rejection? Way down the line, of course, there would have to be a lot of steps between where we are now and anything like that.

There's nothing inherently impossible with this, the devil's in the details though. As they mentioned about the blood, the human body is very sensitive to even a small amount of antigen. Getting the blood 99% clean of antigens isn't clean enough for the human body (blood snobbery!). The problem with scaling this to organs is multi-layered. With blood, we've been studying the antigens for decades and there's only the two of them (three if you include the rhesus factor that gives us +/- blood). The possible number of antigens in organs is much greater. An organ's cells have nuclei of their own (with their own DNA) and are actively producing proteins, any number of which could trigger a reaction. Blood cells however are without a nucleus and do not produce anything that could cause reactions. Another advantage to using this technique with blood is the ability to mix the enzyme with blood and mix/stir/aggitate the solution to promote enzyme activity. Organs, being solid, will not be so easily or quickly changed. This is definitely an issue since organs don't like being outside of a body for very long.

Other research into organ transplantation that's more promising is looking into stripping a donor (let's say heart) of all the muscle cells (containing nuclei) leaving behind the extracellular matrix (nonnucleated connective tissue such as collagen). This is like taking a house down to its studs. This scaffolding can then be used to guide the growth of stem cells taken from the host so that there is no offending tissue. This has been achieved with rat hearts in labs. There's a boat-load of problems still with this, but I feel those are easier to overcome. Another avenue of research involves simply growing an entire replacement organ from the patient's stem cells. This is more difficult, i.e. absence of a pre-existing scaffold. Even this wouldn't be a magic bullet though. If the problem with the original organ is genetically based, growing a new one will just result in a similarly defective organ.

I think the quickest way to see some improvements in organship is to get more people aware of the need for them and get more people to register as donors. Second to that, the system that currently assesses the viability of an organ for transplant needs some reform. People with Cystic Fibrosis that are in the need of a transplant would LOVE to have a pair of lungs from a light smoker or someone that had less than perfect lungs. If your house burned down, you'd choose a sheet-metal shack to live in over a cardboard box after all.

[Darmalus]

There have been big forward strides in using 3d printing to build the extracellular matrix without the need for any original donor organ. Still a ways off from a perfect replacement, but something to look forward too.