Turning Piglets into Personalized Avatars

Ed Yong, The Atlantic, 13 December 2017 https://www.theatlantic.com/science/archive/2017/12/turning-piglets-into-personalized-avatars-for-sick-kids/548204/

Certain diseases have been woefully understudied by the scientific community for a variety of reasons.  Neurofibromatosis type 1 or NF-1, is one such disease that results from mutations in the Neurofibromatosis-1 gene.  Since many different mutations causes the disease, each with their own symptoms, it has been challenging to develop models to study treatment options.  CRISPR could potentially be used to create swine models with the exact mutation of an affected individual allowing for treatments to be screened for their efficacy prior to use in humans.

CRISPR May Not Be a One Size Fits All Therapy

GEN news Highlights, 12 December 2017, https://www.genengnews.com/gen-news-highlights/genetic-differences-could-impact-efficacy-and-safety-of-crispr-therapeutics/81255262

CRISPR has been described as having the potential to revolutionize gene therapy, however innate genetic diversity may hinder mass produced treatments.  Natural variation in DNA sequence among patients indicates that CRISPR therapy may have to be individualized to avoid off-target effects and maximize efficacy.  With the first human CRISPR trials currently ongoing, we may have a better understanding of its therapeutic potential soon.

The Best and Worst of CRISPR Analogies

Rebecca Robbins, STAT, 8 December 2017, https://www.statnews.com/2017/12/08/crispr-analogies-ranked/

Explaining the CRISPR/Cas system can be challenging, especially to those not actively involved in the science.  To help better explain what CRISPR can and cannot do, STAT has ranked the best and worst analogies used across media sources.

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.

CRISPR May Not Revolutionize Mitochondrial Genome Editing

Gammage, P.A.  et. al. (2017) Trends in Genetics. https://www.ncbi.nlm.nih.gov/pubmed/29179920

Mitochondrial DNA has increased in prominence in both biology and medicine as a major player for various diseases.  Attempts to alter the genetic information of mitochondria have made significant advances using zinc finger and TALEN nucleases.  These protein only nucleases are easily delivered into the mitochondria through existing machinery.  While CRISPR has revolutionized genome editing, it is struggling in mitochondria due to the lack of an endogenous mechanism for nucleic acid transport into the mitochondria, preventing its adoption.

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.

New Cas9 Cryo-EM Structure Solved

Huai, C. et. al. (2017) Nature Communications. 8:1375. https://www.ncbi.nlm.nih.gov/pubmed/29123204

Researchers have solved a 5.2 Å cryo-EM structure of Cas9 complexed with sgRNA and target DNA.  The structure found that the HNH domain moves closer to the DNA than previously reported and suggests that this new structure resembles a DNA cleavage-activating structure of Cas9.

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.