Could CRISPR/Cas Claims Inhibit Innovation?

Gray, B.N and Spruill, W.M. (2017) Nature Biotechnology 35:630-633. https://www.ncbi.nlm.nih.gov/pubmed/28700549

The ongoing patent battle between the Broad Institute and the University of California-Berkeley provides difficulties for researchers and companies wishing to develop CRISPR/Cas technology, though this is not the only barrier.  This article describes the broad claims that have been granted or that are being investigated and presents the argument that these claims are overly broad and could limit the genome editing field.

Using Gene Drives to Study Fungal Pathogenicity

GEN News Highlights, 30 October 2017, https://www.genengnews.com/gen-news-highlights/crispr-drives-out-fungal-resistance/81255106

Gene drives have been described as a way to eliminate pests, notably the mosquito, from the environment. However, they are a powerful research tool as well.  Candida albicans can be notoriously difficult to study due to its diploid nature.  By combining a newly discovered haploid C. albicans and CRISPR/Cas gene drive technology, researchers have been able to rapidly create diploid knockouts for study (https://www.ncbi.nlm.nih.gov/pubmed/29062088).  The creation of these mutants could serve to increase the pace of drug discovery to combat this and other fungal pathogens.

The Broad Institute and DuPont Pioneer to Provide CRISPR Licenses

GenomeWeb, 18 October 2017, https://www.genomeweb.com/business-news/broad-dupont-pioneer-partner-provide-non-exclusive-licenses-crispr-ip

DuPont Pioneer and the Broad Institute will provide non-exclusive licenses for their CRISPR/Cas intellectual property to any organization.  These licenses will be provided free of charge to both universities and non-profit organizations involved in academic research.  Notably, the deal does not include gene drives or tobacco products designed for human use.

Engineering the Epigenome

Pulecio, J. et. al. (2017) Cell Stem Cell 21:431-447. https://www.ncbi.nlm.nih.gov/pubmed/28985525

The CRISPR/Cas system has been quickly adopted as a genome editing tool, however recent advances are translating the system to the epigenome.  This protocol review surveys the potential that CRISPR/Cas has to aid research into the impact of chromatin features have on gene expression and cell behavior.

Model Predicts Relationship Between Editing Speed and Off-Target Effects

David Ruth, 17 October 2017, PHYS.org, https://phys.org/news/2017-10-genome-efficient.html

Researchers at Rice University have used computational models to predict the speed at which the CRISPR/Cas system identifies and cleaves the targeted location.  The research, published in the Biophysical Journal (https://www.ncbi.nlm.nih.gov/pubmed/28978436), determined that by allowing CRISPR to cut at off-target sites the system could quickly find and cleave the targeted site.  By limiting the system’s ability to cleave off-target sites, the dissociation of Cas9 from DNA greatly decreased the speed at which on-target sites were identified.

Gold Nanoparticles Deliver CRISPR in Muscular Dystrophy Treatment

Sophia Ktori, GEN News Highlights, 04 October 2017, http://www.genengnews.com/gen-news-highlights/crispr-nanoparticles-repair-duchenne-muscular-dystrophy-gene/81255009

Scientists working on CRISPR delivery have developed a gold nanoparticle that encapsulates the CRISPR/Cas machinery for delivery to cells.  This new technique, coined CRISPR-Gold, was published in Nature Biomedical Engineering (https://www.nature.com/articles/s41551-017-0137-2).  In the paper the authors demonstrated CRISPR-Gold’s ability to correct the mutated dystrophin gene in a mouse model, with mice receiving CRISPR-Gold treatment displaying two-fold improvement in hanging time in a four-limb hanging test, compared to control mice.

CRISPR Delivery in the Ear

Antonio Regalado, MIT Technology Review, 22 September 2017, https://www.technologyreview.com/s/608899/the-easiest-place-to-use-crispr-might-be-in-your-ear/

One of the major challenges with CRISPR based medical therapies is delivering the necessary components.  One group at the Massachusetts Eye and Ear Infirmary are working on delivering the CRISPR/Cas machinery into mice ears to cure a genetic defect that results in gradual hearing loss.  In the best cases the mice retained significant hearing at two months of age.

Chinese Research Team Fix Genetic Disorder in Human Embryos

David Cyranoski, 02 October 2017, Nature News, http://www.nature.com/news/chinese-scientists-fix-genetic-disorder-in-cloned-human-embryos-1.22694

A new report in Protein and Cell (https://www.ncbi.nlm.nih.gov/pubmed/28942539) is the latest in a string of human embryo CRISPR publications.  Using a modified CRISPR/Cas9 system tethered to a second enzyme that can swap individual DNA bases, the researchers targeted an A to G point mutation that results in β-thalassemia.  Eight of the 20 cloned embryos contained a corrected copy of the gene, possibly curing the recessive disorder.  The scientists were careful to point out that not all cells in the embryo were modified, which could have unintended consequences.

New Cas9 Mutations Increase Accuracy

Chen et. al. (2017) Nature. https://www.ncbi.nlm.nih.gov/pubmed/28931002

Researchers using FRET to study previously engineered high-fidelity Cas9 (SpCas9-HF1) and enhanced Cas9 (eSpCas9), identified that these versions are trapped in an inactive state when bound to off-target sites.  Using this observation and rational protein engineering, the researchers made additional modifications to the REC3 domain to prevent activation of the HNH nuclease domain unless the guide RNA and target DNA match is very close.  This new Cas9, coined Hyper Cas9 (HypaCas9) maintains the native Cas9 on target efficiency, but decreases the number of off-target events.

Getting CRISPR into the Body

Emily Mullin, MIT Technology Review, 22 September 2017, https://www.technologyreview.com/s/608898/five-ways-to-get-crispr-into-the-body/

While CRISPR has shown great promise in the lab, its clinical application is more difficult due to delivery challenges.  Researchers are diligently working on this problem, with this article covering five possible ways to deliver the CRISPR/Cas machinery including gels/creams, edible CRISPR, ear injections, skin grafts, and ex vivo therapy.