MilliporeSigma Granted European CRISPR Patent

Alex Philippidis, GEN News Highlights, 07 August 2017, http://www.genengnews.com/gen-news-highlights/milliporesigma-to-be-granted-european-patent-for-crispr-technology/81254776

The European Patent Office has issued a “Notice of Intention to Grant” to MilliporeSigma for CRISPR technology consisting of claims related to single guide gene editing in both cellular and non-cellular systems, including human and mammalian cells, in addition to claims related to therapeutic treatment of a patient.  By issuing this patent the European patent landscape is on its way to becoming as complicated as that of the US.

CRISPR Used to Identify Cancer Immunotherapy Targets

Sophia Ktori, GEN News Highlights, 08 August 2017, http://www.genengnews.com/gen-news-highlights/crispr-screen-identifies-top-100-essential-genes-for-cancer-immunotherapy/81254771

One of CRISPR’s most promising therapeutic uses is in the creation of cancer immunotherapies.  Scientists at the National Institute of Health, working in close collaboration with Feng Zhang of the Broad Institute, developed a CRISPR/Cas9 screen allowing them to test many genes for their effect on T-cell responses.  The results, published in Nature (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature23477.html), identified 100 genes that, upon mutating, impacted resistance to T-cell attack.  This report provides a potential explanation as to why some patients do not demonstrate positive response to immunotherapy treatments and underscores the potential benefits of individualized medicine.

NgAgo Gene Editing Study Retracted

David Cyranoski, Nature News, 03 August 2017 http://www.nature.com/news/authors-retract-controversial-ngago-gene-editing-study-1.22412

The authors of the highly controversial NgAgo gene editing paper published in Nature Biotechnology in May 2016 have issued a retraction.  The original article demonstrated that NgAgo was an Argonaut-based DNG-guided endonuclease that could be used to knock out or replace genes more accurately and with greater versatility than CRISPR/Cas.  After publication, many researchers tried to replicate the results with little success.  The authors retracted the study citing scientists’ inability to replicate the main finding.

Could Natural Variation Limit CRISPR’s Therapeutic Uses?

Ashley Yeager, The Scientist, 31 July 2017, http://www.the-scientist.com/?articles.view/articleNo/49994/title/Human-Genetic-Variation-May-Complicate-CRISPR/

CRISPR has been heralded as a potential treatment for many chronic genetic disorders, however implementing them in the human genome could be harder than first expected.  In a recent Nature Medicine article published by David Scott and Feng Zhang (http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4377.html), guide RNAs for 12 genes related to various diseases were compared to whole genome sequencing data from the Exome Aggregation Consortium and the 1,000 Genomes database.  Scott and Zhang found that the number of off-target sites computationally predicted for guides ranged from 0 to over 10,000 depending on the subject’s individual genetic variation.  This study indicates that genetic screening may be required before CRISPR therapies to ensure that off-target effects are limited.

US Scientists Correct Dominant Mutation in Human Embryos

Pam Belluck, 2 August 2017, New York Times https://www.nytimes.com/2017/08/02/science/gene-editing-human-embryos.html

In a newly published Nature article (https://www.nature.com/nature/journal/vaop/ncurrent/full/nature23305.html), a multinational group of researchers from the United States, South Korea, and China successfully corrected the autosomal dominant mutation HCM, responsible for myocardial disease.  In contrast to previous attempts, this study co-injected the CRISPR/Cas machinery with the sperm which resulted in non-mosaic embryos that could be safely implanted.  Further demonstrating the advances made in this study, full genome sequencing revealed no off-target edits.  While this report demonstrates the potential genome editing has to eliminate genetic disease, more research is required to ensure efficacy along with public discussions over the ethical implications.

Cellectis Wins CRISPR Patent in Europe

Jonathan Wosen, GEN News Highlights, 25 July 2017, http://www.genengnews.com/gen-news-highlights/cellectis-granted-t-cell-crispr-patent-in-europe/81254707

French biotech company Cellectis has been granted a European patent to use CRISPR in T cells valid until 2034.  Cellectis hopes to use this technology to edit T cells for cancer therapy. While other companies are pursuing similar treatments, Cellectis hopes to develop a universal CAR-T cell line that can be widely used without tailoring treatment to individuals.

CRISPR Restores Muscle Function in Mice with Congenital Muscular Dystrophy

Diana Kwon, The Scientist, 17 July 2017, http://www.the-scientist.com/?articles.view/articleNo/49910/title/CRISPR-Restores-Muscle-Function-in-Mice/

A new study published in Nature Medicine (https://www.ncbi.nlm.nih.gov/pubmed/28714989) has demonstrated the potential for CRISPR to restore muscle function in congenital muscular dystrophy type 1A.  Researchers used CRISPR gene editing to cut the DNA in two places, allowing the aberrant region to be removed during DNA repair – effectively creating a normal splice.

Screening for CRISPR Off-Target Sites with NGS Sequencing Chips

Phys.org, 29 June 2017 https://phys.org/news/2017-06-technique-enables-safer-gene-editing-therapy.html

CRISPR gene therapy has the potential to cure many genetic disorders, however the off-target activity of the CRISPR system must be understood before therapies can be deployed.  Scientists at the University of Texas at Austin have developed a technique to screen individuals for off-target sites using NGS chips and custom software called CHAMP, or Chip Hybridized Affinity Mapping Platform.  The authors used this technique to characterize the PAM requirements for the CRISPR molecule called Cascade.

Regulation of CRISPR-Associated Nucleases

Jackson, R.N. et. al. (2017) Current Opinions in Microbiology. 37:110-119. https://www.ncbi.nlm.nih.gov/pubmed/28646675

The CRISPR adaptive immune systems in bacteria and archaea are regulated through a series of checkpoints that prevent the self-targeting of the hosts genetic material.  Understanding the mechanisms of CRISPR regulation may allow for fewer off-target effects during CRISPR gene editing.  This review covers our current understanding of CRISPR regulation and identifies conserved themes.