The CRISPR Journal a new peer-reviewed journal from Mary Ann Liebert, Inc., publishers, announces the publication of its December issue. The Journal is dedicated to validating and publishing outstanding research and commentary on all aspects of CRISPR and gene editing, including CRISPR biology, technology and genome editing, and commentary and debate of key policy, regulatory, and ethical issues affecting the field. The Journal, led by Editor-in-Chief Rodolphe Barrangou, PhD (North Carolina State University) and Executive Editor Dr. Kevin Davies, is published bimonthly online and in print. See http://www.
This press release is copyright Mary Ann Liebert, Inc. Its use is granted only for journalists and news media receiving it directly from The CRISPR Journal. For full-text copies of articles or to arrange interviews with Dr. Barrangou, Dr. Davies, authors, or members of the editorial board, contact Kathryn Ryan
1. #CRISPRbabies: Notes on a Scandal (First Cut)"Like almost everyone, I was stunned by the birth announcement of genetically-modified twins, Lulu and Nana..." So begins a First Cut by Sean Ryder in the December issue of The CRISPR Journal. One of the most important observations in the wave of criticisms that greeted last month's announcement by Chinese researcher He Jiankui of the birth of twins following germline editing centered on the nature of the gene edits themselves. Ryder took to Twitter to highlight the specific gene variants carried by the twins (Lulu and Nana), none of which faithfully replicate the natural variation (the deletion of a 32-base stretch of the gene) reported in the human population. The consequences of these variants have never been modeled in other systems. In this article, Ryder discusses the ramifications of the reported gene edits and his hopes for the future health of the twins at the center of the saga.
Contact: Sean Ryder (UMass Medical School)
2. CRISPR Crossroads for Genome Editing (Editorial)
In the December editorial, Editor-in-Chief Rodolphe Barrangou weighs in on the uproar in Hong Kong following the announcement of twin births by editing human embryos. "The transgressions of a cavalier young scientist have negatively impacted an entire research ?eld. Now is the time to pause and reassess." Barrangou believes the road ahead will require "the involvement of both scientists and nonscientists, including regulators and patients," and action must take place soon. "The ?eld is going too fast and we cannot afford to wait for more misguided experiments to occur while we catch our ethical breath."
Contact: Rodolphe Barrangou (CRISPR Journal/NCSU)
3. Selective maintenance of CRISPR arrays across prokaryotes
Bacteria and other prokaryotes have evolved immune systems including CRISPR to provide defense against constant viral attacks. But why do so many single-celled organisms carry multiple copies of the same type of immune system? Using a comparative genomics approach looking across all prokaryotes, Philip Johnson and colleagues (University of Maryland) find that, on average, organisms are under selective pressure to maintain more than one CRISPR array. Possible reasons include benefits of improved immunity through redundancy and/or increased specialization against specific threats. The authors also suggest a tradeoff between memory span and learning speed could select for both "long-term memory" and "short-term memory" CRISPR arrays.
Contact: Philip Johnson (University of Maryland, College Park MD)
4. Enhancing Homology-Directed Repair (HDR) in Mammalian Cells
CRISPR-Cas gene editing results in two types of DNA repair: non-homologous end-joining (NHEJ) or homology-directed repair (HDR). The former results in various insertions or deletions at the target site, and thus is good for gene inactivation; the latter uses a donor template to engineer a more precise repair, but rates can be very low (<1%). Using an engineered Cas9 and an innovative delivery method, a team at McGill University reports an impressive increase in the rate of HDR, with percentages improved up to 90%. These results suggest that donor DNA biotinylation and Cas9-donor conjugation in addition to delivery technique, significantly influence HDR efficiency.
5. Expanding the CRISPR toolkit for mouse genome editing
Researchers' ability to use CRISPR-Cas to engineer specific gene edits in mouse embryos is limited by the strict sequence requirements of the proto-spacer adjacent motif (PAM) at the target site. In an effort to expand the PAM repertoire for mouse genome editing, the authors tested Cas9 variants from less common sources that target alternative PAM sequences. These alternative nucleases not only recognize a broader range of PAM sites but frequently generated heterozygous alleles in which one copy of the target gene is unmodified.
Contact: Paul Thomas (University of Adelaide, Australia)
6. Safe harbor targeted CRISPR-Cas9 tools for molecular-genetic imaging of cells
Noninvasive molecular-genetic imaging of reporter gene expression is an invaluable approach for monitoring cells in vivo. However, reporter genes are often randomly inserted in the cellular genome, which can cause unwanted downstream effects. To overcome this, John Ronald and colleagues at the Robarts Research Institute in Ontario, Canada, developed a CRISPR-Cas9 tool to specifically edit cells at the AAVS1 safe harbor site to co-express a selection marker and a reporter gene. They used this system to noninvasively track the viability of these genome edited cells over time with molecular-genetic imaging. With further development, the authors suggest, "this CRISPR-Cas9 reporter gene system could be broadly applied to a number of in vivo cell tracking studies."
Contact: John Ronald (Robarts Research Institute, Ontario, Canada)
7. Special Delivery: How CRISPR-Cas Gains Cellular Entry (Review Article)
For all the recent progress in somatic genome editing and expanding the CRISPR toolbox, a major challenge for the use of CRISPR as a therapeutic tool is the question of delivery. Researchers are exploring a variety of ways to target and deliver the CRISPR-Cas9 machinery to specific organs, whether by using a virus, a ribonucleoprotein, or some other type of nanoparticle. In this review article, investigators from the University of California and the Garvan Institute in Australia assess the latest advances in engineering Cas9 and developing therapeutic strategies to improve the prospects of therapeutic CRISPR delivery.
Other Articles in the December 2018 Issue:
First Cut: He said what now?
Kevin Davies (The CRISPR Journal)
Review article: Applications of CRISPR-Cas in Bioengineering, Biotechnology, and Translational Research
Cia-Hin Lau (City University of Hong Kong)
The Phage Whisperer: An Interview with Sylvain Moineau
Kevin Davies & Sylvain Moineau (Université Laval, Quebec, Canada)