CRISPR Digest #12

I know what you’re all thinking. When is she finally going to post about CRISPR again? It’s been too long. Well, you’re absolutely right and I’m going to make up for it. Last week I glimpsed a short article on the Science News site discussing the first CRISPR-modified cabbage. The botanist Stefan Jansson at Umeå University in Sweden “cultivated, grew, and ate a plant that had its genome edited with CRISPR-Cas9”. This is obviously very fitting since one of the pioneers of the technology, Emmanuelle Charpentier, carried out some of the seminal work at the same university between 2009 and 2014.

To cheer you up at the end of the summer, here have a listen to a short radio report on the CRISPR cabbage served with garlic and pasta – it’s in Swedish but that makes it all the more charming.

http://sverigesradio.se/sida/embed?type=publication&id=6508845

On a slightly more serious note though, I wrote about CRISPR gene-editing in the context of HIV infection in a previous post, and want to follow up here. In the last paper I discussed (Kaminski et al, 2016), the authors showed, as a proof-of-principle, that it is possible to use the Cas9 protein to cut out the HIV genome from infected T cells’ genomes, at least in a model of HIV infection. However, following this promising result two papers published more recently (both Wang et al, 2016 – sadly not me) show that the same process actually generates HIV mutants that can become infectious again. In particular, when the Cas9 protein cuts the HIV DNA that is integrated in the human genome, the human cells try to repair the cut in a process called non-homologous end joining (NHEJ). This correction mechanism, however, is prone to making errors and can sometimes lead to the creation of HIV DNA sequences that can replicate again. These HIV DNA sequences could then potentially produce new virus particles that can replicate, start a new round of infection and are, of course, resistant to the original CRISPR/Cas9 targeting, since they now contain new mutations. Once again science proves to be more fickle than originally thought; it really shouldn’t surprise us anymore.

wang-2016

Schematic showing how HIV can escape CRISPR/Cas9 editing – copied directly from Wang et al, 2016, Cell Reports

To return to and end on a more culinary note: not only has the world now seen CRISPR cabbage, but a report (Ren et al, 2016) published a couple of weeks ago demonstrated that the gene-editing technology also works in grapes, Chardonnay to be precise. The scientists modified the gene coding for the L-idonate dehydrogenase protein, which is involved in producing tartaric acid. So it is in theory possible to generate sweeter, or at least less acidic, grapes:

screen-shot-2016-09-18-at-16-17-57

Genome-edited Chardonnay plant – copied directly from Ren et al, 2016

References:

Kaminski R, Chen Y, Fischer T, Tedaldi E, Napoli A, Zhang Y, Karn J, Hu W, Khalili K (2016) Elimination of HIV-1 Genomes from Human T-lymphoid Cells by CRISPR/Cas9 Gene Editing. Scientific Reports 6: 22555

Ren C, Liu X, Zhang Z, Wang Y, Duan W, Li S, Liang Z (2016) CRISPR/Cas9-mediated efficient targeted mutagenesis in Chardonnay (Vitis vinifera L.). Scientific Reports 6: 32289

Wang Z, Pan Q, Gendron P, Zhu W, Guo F, Cen S, Wainberg Mark A, Liang C (2016) CRISPR/Cas9-Derived Mutations Both Inhibit HIV-1 Replication and Accelerate Viral Escape. Cell Reports 15: 481-9

Wang G, Zhao N, Berkhout B, Das AT (2016) CRISPR-Cas9 Can Inhibit HIV-1 Replication but NHEJ Repair Facilitates Virus Escape. Mol Ther 24: 522-526

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s