Gene Editing Update: Genetically Modified Primates Are Here!

Incredible progress in the world of gene editing:

  1. Researchers have successfully generated genetically-modified monkey babies!Image
    If you recall, in an earlier post I mentioned a few types of “molecular cursors” whose job it is to find the right place in the DNA out of the whole genome (using a guide RNA to bring it to the right spot) in order to add or delete certain pieces of DNA. Well, using the newest cursor,  CRISPR/Cas9, collaborators from at Nanjing University, the Yunnan Key Laboratory of Primate Biomedical Research and Kunming Biomed International succeeded in making not one but two different precise genetic mutations at once, and what’s more, they confirmed the absence of off-site mutations at other locations where the single guide RNAs (sgRNAs) could feasibly (albeit poorly) bind, which has been a concern with this particular editing system. The mutated embryos were then implanted into the uterus of a surrogate monkey mother and carried to term. See highly technical “graphical abstract” at right (can’t you just picture an undergrad shrinking, copying and pasting those monkeys?), and pic of the babies below.This is the first time that GM primates have been made–which means that we’re closer than ever (although still very far off, for ethical reasons) to creation of genetically modified humans. But the truly revolutionary thing about this achievement is that now we can study human genetic diseases way more effectively, since humans are obviously more closely related to other primates than to rodents such as mice. And the fact that CRISPR/Cas9 successfully made simultaneous mutations at different genes is particularly exciting, because many human genetic diseases result from a combination of genetic mutations, rather than a single one. Read an article on this paper here, or read the actual paper here.
  2. Fine-tuning of the editing process: A Nature Biotechnology paper was just published on May 18, 2014 (two weeks ago!) that analyzed and improved the accuracy of the CRISPR/Cas9 gene editing system. Many scientists (like the ones performing the monkey gene editing above) predict where Cas9 will bind based on where else the guide RNAs might hybridize with the organism’s DNA, and then test each possible off-site target for mutations one-by-freakin’-one. In contrast, the University of Virginia School of Medicine researchers in this study performed a genome-wide analysis of Cas9 binding using a technique called ChIP-Seq, or Chromatin Immunoprecipitation followed by high-throughput DNA sequencing. This accurately and without bias identified all the locations where Cas9 was binding, because it didn’t depend on the sequence of the sgRNA.Dr. Mazhar Adli and team were able to identify several factors that influence Cas9 binding (read the abstract if you’re interested to know what these factors are), which are already helping scientists everywhere design more effective and precise gene editing experiments. In addition, these researchers found that a certain variant of the Cas9 enzyme, while more difficult to use, is much more accurate and introduces far fewer unintended mutations than the wild type enzyme does. Go science!

Read more than you ever cared to know about CRISPR/Cas9 here.

ImageDiscussion Topic: Dr. Adli from University of Virginia found that ChIP-Seq is highly effective at identifying all genomic locations that Cas9 binds during a given gene editing process. I can imagine this method one day being applied to IVF gene editing treatments–any cultured embryos that show presence of undesired mutations would not be selected for transfer to the mother’s uterus. Such a reliable screening process makes gene editing way safer and more practical. Someday it will be inevitably proven safe and effective in all organisms, even humans, but that’s not to say it will ever be permitted. Does the good of gene editing outweigh the evil? What laws could we put in place to make sure that it does?



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