New Study Finds No Evidence for Genome Editing with NgAgo

Khin, C, N., et. al. (2017) PLOSOne, 12(6):e0178768. https://www.ncbi.nlm.nih.gov/pubmed/28609472

A new study in PLOSOne has found no evidence of gene editing activity with Natronobacterium gregoryi Argonaute (NgAgo).  Previously NgAgo had been described as a DNA targeting, DNA guided endonuclease similar to the CRISPR/Cas system. However, since its first report few labs have been able to duplicate the results.  In this report researchers injected over 100 mouse zygotes with the NgAgo plasmid supplied by AddGene and found no evidence of successful gene editing.

Genome Editing as Therapy for Muscular Dystrophies

Pini, V., et. al. (2017) Current Stem Cell Reports. 3:137-148. https://www.ncbi.nlm.nih.gov/pubmed/28616376

Muscular Dystrophy is one of the many diseases scientists are evaluating for treatment with CRISPR/Cas systems with many labs reporting new findings.  This review provides a survey of current findings and the impact they may have on Muscular Dystrophy treatments.

Jennifer Doudna Talks CRISPR on Sunday Night with Megyn Kelly

Sunday Night with Megyn Kelly, NBC, 11 June 2017, http://www.nbcnews.com/megyn-kelly/video/life-changer-965215299885

On Sunday Night with Megyn Kelly, Jennifer Doudna describes how the CRISPR system functions and how she got her start in science.  The piece doesn’t stop there but travels around the country interviewing different researchers working in plant science and human health demonstrating the potential the CRISPR system has to drastically change the human experience.

Genome Editing in Mammals

Fernandez, A., et. al. (2017) Mammalian Genome. https://www.ncbi.nlm.nih.gov/pubmed/28589393

Genome editing began in mammals with the development of Zinc Finger Nucleases and has since become an invaluable tool with the discovery of the CRISPR/Cas9 system.  This review article covers how gene editing technology has been applied to mammals and how far the technology has evolved.

Optimizing sgRNA Design

Kuan, P.F. et. al. (2017) BMC Bioinformatics, 18:297 https://www.ncbi.nlm.nih.gov/pubmed/28587596

Design of sgRNAs can prove challenging due to the tendency of RNA to form complex secondary structures and different sequences imparting different thermodynamic properties.  By using a machine learning approach and previous oligonucleotide design and models, Kuan et al. analyzed CRISPR datasets to create an R package, predictSGRNA, to help with sgRNA design.

CRISPR Startups Fight Back Against CRISPR Off-Target Report

Antonio Regalado, 9 June 2017, MIT Technology Review, https://www.technologyreview.com/s/608073/gene-editing-companies-hit-back-at-paper-that-criticized-crispr/

In response to the Nature Methods Letter outlining potential off-target effects introduced by CRISPR/Cas9 genome editing, Intellia Therapeutics and Editas medicine have penned separate letters to the journal outlining their concerns with the report.  Nessan Bermingham, CEO of Intellia, went so far as to call on Nature Methods to retract the Letter, “given the issues around the design and interpretation.”  Nature Methods has stated that they are considering the concerns and discussing them with the authors.

Cloud-Based Deconvolution Software for CRISPR Pooled Screens

Jeong, H.H. et. al. (2017) Bioinformatics, btx335. https://www.ncbi.nlm.nih.gov/pubmed/28541456

Analyzing next generation sequencing data from pooled screening experiments can be a difficult and time-consuming process, with few programs providing a user-friendly interface and presentation of data.  Researchers from the Texas Children’s Hospital have developed a cloud based system for analysis, deconvolution, and presentation of sequencing data – allowing researchers to quickly determine the frequency and types of mutations.

Explaining CRISPR in Ever More Complicated Ways

Wired, 24 May 2017, https://www.wired.com/video/2017/05/biologist-explains-one-concept-in-5-levels-of-difficulty-crispr/

Nevill Sanjana, biologist at New York University and the New York Genome Center, explains CRISPR to a child, teen, college student, graduate student, and post-doctoral researcher increasing the level of complexity each time.

CRISPR Off-Target Affects May be Greater than Previously Assumed

EurekAlert, Columbia University Medical Center Press Release, 29 May 2017, https://www.eurekalert.org/pub_releases/2017-05/cumc-cge052617.php

Since its discovery, the CRISPR/Cas9 system has been on an unprecedented pace towards clinical use, though a new Nature Letter may slow down this process.  In the letter, Unexpected mutations after CRISPR-Cas9 editing in vivo (https://www.ncbi.nlm.nih.gov/pubmed/28557981), researchers completed whole genome sequencing of CRISPR edited mice and discovered 1,500 single nucleotide mutations and greater than 100 larger deletions and insertions with none of the off-target mutations predicted by computer algorithms.  While this study could change the way CRISPR therapies progress, further researcher is needed to confirm the results.

Proximal Targeting With dCas Alters Chromatin Structure Allowing Genome Editing

Chen, Fuqiang, et. a. (2017) Nature Communications. 8:14958. https://www.nature.com/articles/ncomms14958

Many different Cas variants have been discovered, each with slightly different activities.  Francisella novicida Cas9 (FnCas9) is one such Cas variant. It is frequently inhibited at genomic loci, presumably due to chromatin formation.  By using dead SpCas9 to target proximally, FnCas9 could cleave at the target site, presumably due to chromatin rearrangements.