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February 15, 2018

New Journal Details Applications, Technology Behind CRISPR Gene Editing

The CRISPR Journal Aims to Offer Original Research Papers, Commentaries, and Articles on Issues in the Field

New Journal Details Applications, Technology Behind CRISPR Gene Editing

The CRISPR Journal, which will publish its inaugural issue today, highlights research on the applications and underlying technology of CRISPR gene editing.

  • The CRISPR Journal, an international, multidisciplinary peer-reviewed journal, will publish its inaugural issue today, with the goal of highlighting outstanding research on the myriad applications and underlying technology of CRISPR (clustered regularly interspersed short palindromic repeats) gene editing.

    Published by GEN publisher Mary Ann Liebert Inc., The CRISPR Journal has been established to offer cutting-edge international original research papers, as well as a compelling mix of review articles, perspectives, profiles, and commentary spanning matters of research as well as social, ethical, and business issues confronting the field.

    “This is obviously a very momentous time for the field, and this inaugural issue fittingly captures the breadth and depth of the field, spanning plant editing, gene drives, and therapeutic applications, as well as an IP landscape review and historical insight into the genome editing revolution,” Rodolphe Barrangou, Ph.D., editor-in-chief of The CRISPR Journal, said in a statement.

    “The cover illustrates the ceremonial ribbon cutting in a relevant manner, and our content showcases our commitment to a diverse readership,” added Dr. Barrangou, who is also associate professor of food science, North Carolina State University.

    Dr. Barrangou is among the CRISPR luminaries published in the journal. Others include Qin Liu, Ph.D., M.D., of Massachusetts Eye and Ear Infrmary and Harvard Medical School; Francisco Mojica, Ph.D., of University of Alicante in Spain; Luke A. Wiley, Ph.D., of University of Iowa and its Carver College of Medicine; Jacob Sherkow, J.D., an intellectual property lawyer at New York Law School; Fyodor Urnov, Ph.D., of the Altius Institute for Biomedical Sciences; and Eduard Akhunov, Ph.D., of Kansas State University.

  • "Flexible Tool"

    In this inaugural issue, Dr. Akhunov and colleagues published their findings from generating heritable mutations in the TaGW2, TaLpx-1, and TaMLO genes of hexaploid wheat, through application of CRISPR/Cas9-based multiplexed gene editing built by combining tandemly arrayed transfer RNA (tRNA)–guide RNA (gRNA) units. Consistent with results previously reported in rice and maize, Dr. Akhunov’s team reported demonstrating that heritable mutations in multiple gene targets in the wheat genome can be induced using a construct with an array of the gRNA–tRNA units driven by a single promoter.

    “The MGE approach provides a fexible tool for implementing complex gene-editing strategies in wheat where the majority of genes have at least three homoeologous copies,” Dr. Akhunov and colleagues observed in “Transgenerational CRISPR-Cas9 Activity Facilitates Multiplex Gene Editing in Allopolyploid Wheat.” “By designing gRNAs to the targets carrying homoeolog-specific sites or to the conserved targets identical in all three wheat genomes, it should be possible either to edit multiple genes from a specific genome selectively, or to introduce modifications into all duplicated gene copies.”

    The study was one of four research articles featured in The CRISPR Journal. In another article, Dr. Liu and colleagues detailed results from a spacer-mediated, allele-specific CRISPR/Cas9 genome-editing approach targeting a single-nucleotide mutation in rhodopsin (Rho)-P23H mice, a model of dominant retinitis pigmentosa. The approach used both SpCas9 variants and truncated single-guide RNAs (sgRNAs).

    “We demonstrated that an in vivo allele-specific genome-editing approach based on sequence differences in the spacer region of the sgRNA can selectively inactivate a single-base missense dominant allele at its native locus in the RHO-P23H knock-in mouse model of [autosomal dominant retinitis pigmentosa],” Dr. Liu and colleagues concluded in “Allele-Specific CRISPR-Cas9 Genome Editing of the Single-Base P23H Mutation for Rhodopsin-Associated Dominant Retinitis Pigmentosa.” "By allowing for targeting of mutations that occur outside of PAM [protospacer adjacent motif] sequences, this approach significantly broadens the potential application of allele-specific CRISPR/Cas9 genome editing for the treatment of dominant genetic diseases.”

    Dr. Wiley and colleagues at the University of Iowa’s Stephen A. Wynn Institute for Vision Research reported on the successful use of CRISPR/Cas9 homology-dependent repair of a common mutation in the gene CLN3 in induced pluripotent stem cells (iPSCs) from two patients with Batten disease (juvenile neuronal ceroid lipofuscinosis). Approximately 85% of patients with Batten disease harbor at least one allele containing the mutation, a 1.02kb genomic deletion spanning exons 7 and 8.

    “These data represent important proof of concept in generating gene-corrected, patient-derived iPSCs for disease modeling and treatment of Batten disease,” Dr. Wiley and colleagues stated in “CRISPR-Cas9-Mediated Correction of the 1.02 kb Common Deletion in CLN3 in Induced Pluripotent Stem Cells from Patients with Batten Disease.”

    The study also noted that there is no FDA-approved treatment for Batten disease: “The creation of CRISPR-corrected patient iPSCs helps mitigate this dearth by providing investigators with genetically matched, isogenic control cell lines.”

  • Addressing Dearth of Treatments

    Philippos Aris Papathanos, Ph.D., of the University of Perugia in Italy, and Nikolai Windbichler, Ph.D., of Imperial College London, detailed their development of the redkmer computational pipeline, designed to identify short and highly abundant sequence elements occurring uniquely on the X chromosome, suitable for targeting by CRISPR endonucleases. The shredding of the X chromosome during male meiosis through CRISPR-based synthetic sex-ratio distorters offer a promising avenue for area-wide control of harmful insect pest or disease vector species, the researchers noted.

    Redkmer was designed for use with minimally processed whole-genome sequence (WGS) data from males and females. The researchers tested redkmer with short- and long-read WGS data of Anopheles gambiae, the major vector of human malaria, in which the X-shredding paradigm was originally developed.

    “A combination of single-molecule and long-read sequencing, when combined with short-read WGS data from males and females, can be used to identify X-chromosome-specific sequences efficiently and reliably, which can be used to develop X-shredder-based sex-ratio distortion systems,” Drs. Papathanos and Windbichler concluded in “Redkmer: An Assembly-Free Pipeline for the Identification of Abundant and Specific X-Chromosome Target Sequences for X-Shredding by CRISPR Endonucleases.”

    The complete first issue of The CRISPR Journal can be read on its website.

    “The debut issue of The CRISPR Journal features a wonderful breadth and overall quality that fully measures up to our hopes and expectations when we announced the Journal nine months ago,” added Kevin Davies, Ph.D., executive editor of The CRISPR Journal and vice president of strategic development at Mary Ann Liebert, Inc. “From CRISPR patents to conservation, gene therapy to plant gene editing, immune responses to bioinformatics, and a stunning review on the history of genome editing ‘before CRISPR,’ we think the launch issue captures the excitement and importance of this remarkable field.”

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