CRISPR Converts Microbes to Tape Recorders

GEN News Highlights, 27 Nov 2017, https://www.genengnews.com/gen-news-highlights/crisprcas-used-to-create-microscopic-data-recorder/81255201

Scientists have created a CRISPR/Cas system in E. coli that allows for the recording of events and the time at which they occurred.  This was done by having the cell insert CRISPR spacers at regular occurring sets of time, however when a signal was detected the bacteria would insert a signal sequence instead.  This locus can then be read using pre-existing sequencing tools providing a readout of events.  The researchers hope this technology could be used to record biological events.

Increasing the Potency of T Cell Cancer Therapy

GEN News Highlights, 21 November 2017, https://www.genengnews.com/gen-news-highlights/crispr-editing-creates-tcr-swap-shop-for-cancer-immunotherapy/81255191

In the United Kingdom, Cardiff University researchers have used CRISPR to create T cells up to a thousand times more sensitive to cancer cells.  These cells have been edited to remove their own T-cell receptors, leaving only those targeting cancer cells.  The hope is that custom immunotherapies such as this may one day replace conventional cancer therapies.

Are Gene Drives Too Risky?

Carl Zimmer, The New York Times, 16 Nov 2017. https://www.nytimes.com/2017/11/16/science/gene-drives-crispr.html

Kevin Esvelt of Harvard University was one of the first to put forth the idea of using gene drives to save endangered wildlife from extinction by reducing/eliminating invasive animals.  Now Dr. Esvelt has published a new article on bioRxiv in which he presents mathematical models that describe what could happen after the release of a gene drive, even for field trials.  These models detail what Dr. Esvelt is calling an unacceptable risk of the altered genes spreading to locations where the targeted species is not invasive.  The authors were careful to emphasize that disease eliminating gene drives, such as those proposed to eliminate malaria, should still be considered as this would allow the rapid elimination of disease carrying vectors across wide areas.

Gene Drives Could Aid New Zealand’s War on Rats

Ed Yong, The Atlantic, 16 Nov 2017. https://www.theatlantic.com/science/archive/2017/11/new-zealand-predator-free-2050-rats-gene-drive-ruh-roh/546011/

Invasive predators have long been devastating to New Zealand’s native birds, notably the flightless giant kakapo parrot and kiwi .  Through Predator-Free 2050, New Zealand is aiming to eliminate invasive rats, possums, and stoats.  One possible mechanisms may be a CRISPR gene drive that allows rapid proliferation of detrimental genes through a population without harming other animals like traditional pesticide methods.

Automated Screening for CRISPR Mutations

Steve Siembieda and Kyle Luttgeharm, GEN Tutorials, 1 Nov 2017. https://www.genengnews.com/gen-articles/rapid-screening-for-the-zygosity-of-crispr-mutations/6194

Screening for CRISPR edits remains a large bottleneck in the gene editing process.  This GEN tutorial walks through a novel method for simultaneously identifying clones containing edits, while predicting the zygosity of the mutation in diploid organisms.  The assay relies on statistical models that predict the frequency of heteroduplex formation versus duplex formation and a T7 Endonuclease I based cleavage assay coupled with the quantitative abilities of capillary electrophoresis.

How Easy is CRISPR Technology, Really?

Annie Sneed, Scientific American, 02 November 2017, https://www.scientificamerican.com/article/mail-order-crispr-kits-allow-absolutely-anyone-to-hack-dna/

Almost every CRISPR article describes its ease of use. With DIY CRISPR kits available by mail, one reporter set out to determine how easy CRISPR really is.  In this article, published by Scientific American, Annie Sneed attempts CRISPR in her kitchen, a community lab in Santa Clara, and finally meets with a professional scientist from the University of California-Berkeley in order to determine just how easy gene editing really is.

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.

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.