CRISPR Digest #3

First post of the new year, so it only makes sense to go back to one of my favourite topics: CRISPR. As you can imagine, the recent breakthrough in applying the CRISPR technology and not merely using it in basic research has sparked a large patent dispute. Although Jennifer Doudna and Emmanuelle Charpentier originally recognised the method’s potential, it is Feng Zhang who won a large patent over the technology last year (discussed in detail here). However, as far as I understand it, a legal process will be launched in which it may still be possible to reverse the patent ownership. And this would have implications for the various biotechnology start-ups, including Editas Medicine (founded by Zhang, Doudna and others; although Doudna is no longer involved with this company) and CRISPR Therapeutics (founded by Charpentier and others), that were recently launched to utilise CRISPR in therapeutic approaches. I agree with Charpentier when she says that “things are happening fast, maybe a bit too fast”, but she also seems confident that “the story is going to end up well”. According to either John Lennon, Fernando Sabino or an Indian proverb “In the end, everything will be okay. If it’s not okay, it’s not yet the end.” That must be a comforting thought when many millions of dollars are at stake.

But it is not only biotechnology start-ups that have a vested interested in CRISPR technologies. For example, the pharmaceutical company Novartis has recently released information about its attempts to use genome-editing to increase the efficacy of immunotherapy approaches – the use of immune cells, such as “killer T cells”, to treat cancers by instructing them to target malignant cells – in the treatment of haematological cancers.

Following on from the last digest (Hu et al. (2014)), more research groups are using CRISPR to investigate the interactions between HIV and human cells. In one paper (Wang et al. (2014)) they managed to disrupt CCR5, one of the main cell surface receptors of HIV-1, leading to the generation of HIV-resistant cells.

Lastly, CRISPR is being adopted as a tool by researchers in ever more diverse fields of study. For example, in addition to crop plants and HIV, a very recent paper (Peng et al. (2015)) shows the use of CRISPR in Trypanosoma cruzi, the causative agent of human Chagas disease, and a relative of Trypanosoma brucei, the causative agent of human sleeping sickness and nagana in cattle. Yet another group (Kistler et al. (2014)) used CRISPR to engineer the genome of the mosquito Aedes aegypti, the transmitter of yellow fever and dengue viruses. These advances, although at the moment “only” representing proof-of-principle experiments, may in future lead to more effective methods of interfering with the virulence of these protozoan parasites and virus vectors (both images from the Centers for  Disease Control and Prevention):

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References:

Hu WH, Kaminski R, Yang F, Zhang YG, Cosentino L, Li F, Luo BA, Alvarez-Carbonell D, Garcia-Mesa Y, Karn J, Mo XM, Khalili K (2014) RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection.Proceedings of the National Academy of Sciences of the United States of America 111: 11461-11466

Kistler KE, Vosshall LB, Matthews BJ (2014) Genome-engineering with CRISPR-Cas9 in the mosquito Aedes aegypti. 

Peng D, Kurup SP, Yao PY, Minning TA, Tarleton RL (2015) CRISPR-Cas9-Mediated Single-Gene and Gene Family Disruption in Trypanosoma cruzi. mBio 6

Wang W, Ye C, Liu J, Zhang D, Kimata JT, et al. (2014) CCR5 Gene Disruption via Lentiviral Vectors Expressing Cas9 and Single Guided RNA Renders Cells Resistant to HIV-1 Infection. PLoS ONE 9(12): e115987.

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