17 November 2009

Converting RBC Blood Groups by Cleaving Terminal Sugars

It struck me in class today that, with an enzyme to cleave either the A or B sugar from the end of the blood group glycolipid, you could create a 'O' erythrocytes from A, B, or AB individuals, expanding our supply of 'universal donor' blood while drastically reducing the risk of accidental mismatch.

As it turns out, I was not the first to have this idea - way back in 1983, it was demonstrated that a galactosidase derived from coffee beans is able to convert B RBCs into O, and that these cells are viable in people of any blood type (excluding the Bombay phenotype). Unfortunately, this method, and many others attempted for both A and B sugars, required a prohibitively large amount of enzyme and incompatable conditions, preventing its practical large scale use.

Recently (2007), researchers, doing a large scale scan of bacterial and fungal isolates, isolated two novel galactosidases which remove the A and B sugars much more efficently, and with identical, neutral pH, reaction conditions - allowing for the conversion of AB eyrithrocytes as well as A and B. Standard typing showed full conversion of any of the groups to O.

With a quick search, I wasn't able to find any more information on more progess towards making this a reality in blood banks, but hopefully someone's working on it...

References:

Liu Q, Sulzenbacher G, Yuan H, Bennett E, Pietz G, Saunders K, Spence J, Nudelman E, Levery S, White T, Neveu J, Lane W, Bourne Y, Olsson M, Henrissat B, Clausen H (2007). "Bacterial glycosidases for the production of universal red blood cells". Nat Biotechnol 25 (4): 454

Group B erythrocytes enzymically converted to group O survive normally in A, B, and O individuals. Goldstein, Jack; Siviglia, Geraldine; Hurst, Rosa; Lenny, Leslie; Reich, Lilian, Science (1982), 215(4529).

6 comments:

  1. This is a pretty interesting idea. It would be really cool if this would some day become a reality. By expanding our blood banks carring the "universal donor" blood it would allow more people to use them. It is interesting that the idea was thought up in the 80s and people are slowly making it work. I just don't understand why this type of information was kept hidden from everyone.

    ReplyDelete
  2. Interesting...thats a great little find there. There is probably a lot of safety analysis that has to be done before the process gets stream lined. Certainly a lot of potential to have things go wrong, it would seem. Hopefully it will work, though!
    I entertained a side thought on that subject...what if there were a mechanism to fix the transferase that is absent in those with the Bombay phenotype such as through gene therapy or enzyme replacement? This would actually be a bad idea, however, because those individuals would have already made anti-O, A, and B antibody, and thus would destroy their own cells!

    ReplyDelete
  3. This is a really interesting post. I wonder what the business model looks like. Blood is an interesting "product" because of its relatively short shelf life (~35 days for whole blood). To generate the amount of enzyme needed to treat any significant amount of blood probably requires large scale production and is fairly costly. It seems that it would be useful, however, in certain regions of the world where type O blood is uncommon.

    ReplyDelete
  4. Steve, your point is well taken. Do you think that you could combine the gene therapy with exchange transfusion at the time of the gene transfer? I don't know if that would be practical. Probably not, you'd still have the anti-O B cells. Hmmm.... OK, back to the drawing board.

    ReplyDelete
  5. Alternatively, if you could find an enzyme to cleave the 'H' sugar, you could just make your own Bombay blood from O, and use that for a transfusion.

    ReplyDelete
  6. Interesting find. It would be hard to design an enzyme that cleaved to such a high degree of specificity, any kinetics changes could cause non-specific reactions to occur (heat, buffer, concentrations, etc.). Even if the process could be controlled well enough removal of the enzyme is necessary before infusion, it would be nice to see some good old fashion inactivation and purification biochemistry, but might make the whole thing a bit costly.

    ReplyDelete