CRISPR Digest #8

Time for an update. Over the summer the Innovative Genomics Initiative (IGI) hosted a one-week CRISPR workshop where various speakers held lectures addressing how they are using the technology in their research and how they propose to proceed with it. IGI made these lectures available here and had, among others, Jennifer Doudna speak about her group’s work on the mechanism of CRISPR/Cas9:

More recently and perhaps a little more excitingly, researchers led by Feng Zhang at the Broad Institute in Cambridge (USA) have published a paper (Zetsche et al., 2015) describing a new protein – called Cpf1 – from the bacterial species Acidaminococcus and Lachnospiraceae that can also cut DNA, like the now widely used Cas9 protein. However, it acts slightly differently from Cas9 in that it only needs a single guide RNA to find its target DNA and importantly, it cuts the DNA in a way that leaves so-called “sticky ends”. These cut sites with “staggered” ends allow much more controlled insertion of new DNA into the cut site. This, in turn, means that cells can now be more easily made to express engineered proteins with specific mutations, for example, or corrected versions of proteins. Although this was possible using the original CRISPR/Cas9 system it was not very efficient. However, pictures supposedly say more than a thousand words so here is their “graphical abstract”…

Graphical abstract of how Cpf1 can target DNA with the help of a single guide RNA - copied directly from Zetsche et al., 2015

Graphical abstract of how Cpf1 can target DNA with the help of a single guide RNA – copied directly from Zetsche et al., 2015

Lastly, I just want to mention that I have noticed that the original two pioneers of CRISPR technology, Emmanuelle Charpentier and Jennifer Doudna and their research teams, are sticking to basic research. That is to say they study the exact mechanisms by which CRISPR/Cas9 works, elucidate the atomic structures of these protein-RNA-DNA complexes and are still looking for other related systems to better understand how bacteria protect themselves from infections by plasmids (circular bits of DNA) and bacteriophages (viruses that infect bacteria). Despite the high-profile patent case they are involved in and all the other labs around the world that are now using this technology in various applications, such as gene therapy or plant engineering, they remain focussed on simply increasing our knowledge of nature, which I find laudable.

Reference:

Zetsche B, Gootenberg Jonathan S, Abudayyeh Omar O, Slaymaker Ian M, Makarova Kira S, Essletzbichler P, Volz Sara E, Joung J, van der Oost J, Regev A, Koonin Eugene V, Zhang F (2015) Cpf1 Is a Single RNA-Guided Endonuclease of a Class 2 CRISPR-Cas System. Cell (in press).

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2 thoughts on “CRISPR Digest #8

  1. Hi, I am QIngbo, from The University of Tokyo, Japan.
    Thanks a lot for reading this comment despite your busy schedule.
    I study the fundamental mechanism of CRISPR/Cas genome editing, and I have been a big fan of your blog for long!!

    And as a result, I made up my mind to apply for Crick Ph. D program this year.
    (I will be graduating my Univ. in Japan next March, and thinking of entering Crick next September.)

    Hence I would like to ask several questions about the Ph. D life there as well as the application process.
    (Such as how many Asian students are there etc..)
    Would you mind taking time to give me a favor? It would be really appreciated.
    If you have time, please give me an email. Thank you!

    Hope to hear from you back!!

    (P.S Congratulations to Dr.Tomas Lindahl for winning the NobelPrize!!)

    Qingbo Wang
    The University of Tokyo, Faculty of Science,
    Department of Bioinformatics and Systems Biology, Kumiko UI-TEI Lab

    Like

    • Dear Qingbo,
      Thank you for your comment – of course I’d be happy to answer your questions. You can reach me at victoria.wang@crick.ac.uk.
      As far as I know no group at the Crick is directly researching the CRISPR systems from a basic research point of view. However, several labs are of course using it in various applications.
      Best wishes,
      Victoria

      Like

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