Journal Archive

Editorial

Advances & challenges of using CRISPR-Cas9 gene editing for treating Duchenne muscular dystrophy

Spotlight Article

Editorial

Dominique L Ouellet, Benjamin Duchêne, Jean-Paul Iyombe-Engembe & Jacques P Tremblay

Gene Editing Technologies

Genome editing with the CRISPR/Cas9 system has recently been used as a promising strategy to treat Duchenne muscular dystrophy (DMD) both in vitro and in vivo. This editorial provides an overview of the advances and challenges associated with translating this gene editing technology into clinical use to treat DMD.

DOI: 10.18609/cgti.2017.003
Citation: Cell Gene Therapy Insights 2017;3(1), 53-58.

Open access

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In vivo genome editing as a therapeutic strategy for treatment of inherited retinal dystrophies: how close are we to realization?

Spotlight Article

Editorial

Knut Stieger

Gene Editing Technologies

Knut-Stieger

Inherited retinal dystrophies are a heterogeneous group of genetic diseases for which currently no effective treatment strategies exist. Gene editing as a therapeutic strategy for these diseases are currently being studied and this editorial provides an overview of the various in vivo gene editing approaches developed for the treatment of inherited retinal dystrophies.

DOI: 10.18609/cgti.2017.004
Citation: Cell Gene Therapy Insights 2017;3(1), 47-52.

Open access

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Commercial Insights

Cell & Gene Therapy Commercial Insight – January 2017

Mark Curtis & Richard Philipson

Providing a critical overview of the sector’s commercial developments – M&As, licensing agreements & collaborations, financial results, IPOs and clinical/regulatory updates, with commentary from our Expert Contributors.

CELL THERAPY:

It was a busy start to 2017 with multiple new immunotherapy products en route to the clinic. Kite submitted an IND for KITE-718, a TCR technology targeted to MAGE antigens that will be deployed for multiple solid tumor indications. Adaptimmune had an IND accepted for a TCR, also targeted to MAGE. On this front GSK also nominated its second target from Adaptimmune (PRAME) under its collaboration agreement signed back in 2014. Adaptimmune will bring the technology to IND readiness, after which it will be handed off to GSK to complete development. Cellectis submitted an IND for a gene-edited CAR product (UCART123) that will be targeted to AML and BPCDN, the first IND filing for an off-the-shelf T-cell product in the USA. Cellectis’ product wasn’t the only first in the USA though, NantKwest made headlines delivering the first off-the-shelf, engineered NK cell product into the clinic (haNK), which, like Kite and Adaptimmune’s products, will be targeted to solid tumors. It’s clear the race this year will be to demonstrate efficacy data in solid tumors, rather than liquid.

GENE THERAPY:

This month sees several companies advancing their programs by achieving important regulatory milestones, including Rare Pediatric Disease status for Lysogene’s AAV-based treatment for GM1 gangliosidosis, Orphan Drug Designation in Europe for Abeona’s AAV-based treatment for San Filippo B, and Fast Track Designation in the USA for Fibrocell’s autologous, fibroblast-based gene therapy treatment for dystrophic epidermolysis bullosa. Spark Therapeutics continues to release positive news on an almost monthly basis, with the announcement that a $15 million milestone payment has been triggered, and Sarepta Therapeutics builds on the recent approval of its exon-skipping therapy for Duchenne muscular dystrophy with the announcement of a research collaboration with Nationwide Children’s Hospital, where they will work together on their microdystrophin program, as well as another form of gene therapy.

DOI: 10.18609/cgti.2017.007
Citation: Cell Gene Therapy Insights 2017; 3(1), 1-7.

Open access

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Interview

Gene editing of peripheral blood T cells for cancer immunotherapy

Spotlight Article

Interview

Gene Editing Technologies

Dr Avery Posey

Avery-Posey

Dr Avery Posey is an immunologist with training in bioinformatics, biochemistry, and molecular and developmental genetics. He completed his postdoctoral training in the Center for Cellular Immunotherapies at the University of Pennsylvania with Dr Carl H. June investigating novel CAR T cells for solid tumors; CAR T cell costimulation, signaling and metabolism; and cancer-specific glycosylation. Dr. Posey’s work was the first to target the combination of abnormal glycosylation and tumor-associated antigens as a method to avoid off-tumor, on-target toxicities. His laboratory focuses on the development of glycan-specific adoptive cell therapies for the treatment of metastatic and advanced cancers, as well as methods to improve the efficacy and impact of current cellular therapies, including gene editing and overcoming T cell exhaustion.

DOI: 10.18609/cgti.2017.002
Citation: Cell Gene Therapy Insights 2017; 3(1), 43-46.
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The scope and challenges of visualizing CRISPR-Cas9 gene editing in real time

Spotlight Article

Interview

Gene Editing Technologies

Dr. Krishanu Saha

Avery-Posey

Dr. Krishanu Saha is an Assistant Professor in the Department of Biomedical Engineering at the University of Wisconsin-Madison. He is also a member of the Wisconsin Institute for Discovery in the bio-nanocomposite tissue engineering scaffolds theme. Prior to his arrival in Madison, Dr. Saha studied Chemical Engineering at Cornell University and at the University of California in Berkeley. In 2007, he became a Society in Science: Branco-Weiss fellow in the laboratory of Professor Rudolf Jaenisch at the Whitehead Institute for Biomedical Research at MIT and in the Science and Technology Studies program at Harvard University with Professor Sheila Jasanoff in Cambridge, Massachusetts. His research vision is to develop new human stem cell models and therapies using novel biomaterials and genetic engineering techniques. His laboratory uses both experimental and computational approaches to generate new cells, organoids and tissues from patient samples, as well as a suite of gene editing technologies to knockout, correct or insert transgenes into human cells. Major thrusts of his lab are on cell engineering of cell types found in the retina, central nervous system and blood.

DOI: 10.18609/cgti.2017.009
Citation: Cell Gene Therapy Insights 2017; 3(1), 59-62.
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Expert Insight

Current gene editing strategies for the mucopolysaccharidoses

Spotlight Article

Expert Insight

Mark J Osborn, Dok Hyun Yoon, Beom Hee Lee, Chong Jai Kim & Jakub Tolar

Gene Editing Technologies

The mucopolysaccharidoses are one of the subclassifications of a group of metabolic disorders termed lysosomal storage disease. They occur from mutations to genes encoding enzymes responsible for glycosaminoglycan degradation. The ramifications of glycosaminoglycan accumulation are far reaching and result in pathology in multiple organ systems. Because storage diseases are monogenic disorders they are ideal candidates for gene and cell therapy. Importantly, cells distant from the site of enzyme production can benefit from secreted enzyme. Strategies for functionally restoring gene expression include gene therapy and gene editing. The latter employs tailored reagents (zinc finger nucleases, meganucleases, transcription activator-like effector nucleases and clustered regularly interspaced short palindromic repeats/Cas9) capable of generating DNA breaks at user-defined sites. Break resolution by homologous recombination can result in sequence modification for proper, or enhanced, gene expression. This powerful approach holds tremendous promise and here we discuss the employment of programmable nucleases to achieve therapeutic levels of enzyme for treating the pathogenic spectrum of mucopolysaccharidoses.

Submitted for review: Sep 29 2016 Published: Feb 8 2017
DOI: 10.18609/cgti.2017.001
Citation: Cell Gene Therapy Insights 2017;3(1), 17-31.
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Repurposing CRISPR-Cas systems as DNA-based smart antimicrobials

Spotlight Article

Expert Insight

Rodolphe Barrangou & David G Ousterout

Gene Editing Technologies

The molecular machines from CRISPR-Cas immune systems provide versatile platforms for programmable targeting of DNA, which is commonly used to edit eukaryotic genomes, transcriptomes and epigenomes. Recently, CRISPR-Cas systems have been repurposed as specific antimicrobials, given their ability to selectively target and degrade bacterial DNA. Endogenous Cas nucleases can be redirected against pathogenic bacterial chromosomes using self-targeting CRISPR arrays to drive highly specific programmed cell death through targeted DNA damage. Likewise, complete CRISPR-Cas systems can be delivered to bacteria responsible for infectious disease to drive the genesis of lethal DNA breaks. Here, we discuss the various CRISPR-Cas systems and their potential exploitation to create weaponized phages as vectors for effective and selective eradication of bacterial pathogens. This opens new avenues for infectious disease therapies and the engineering of microbiome composition, while addressing the challenges inherent to broad-spectrum antibiotics, enabling selective eradication of pathogens and preventing the selection for antibiotic resistance.

Submitted for review: Feb 9 2017 Published: Apr 25 2017
DOI: 10.18609/cgti.2017.008
Citation: Cell Gene Therapy Insights 2017;3(1), 63-72.
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Recent advances in the use of ZFN-mediated gene editing for human gene therapy

Spotlight Article

Expert Insight

Srinivasan Chandrasegaran

Gene Editing Technologies

Targeted genome editing with programmable nucleases has revolutionized biomedical research. The ability to make site-specific modifications to the human genome, has invoked a paradigm shift in gene therapy. Using gene editing technologies, the sequence in the human genome can now be precisely engineered to achieve a therapeutic effect. Zinc finger nucleases (ZFNs) were the first programmable nucleases designed to target and cleave custom sites. This article summarizes the advances in the use of ZFN-mediated gene editing for human gene therapy and discusses the challenges associated with translating this gene editing technology into clinical use.

Published: Feb 8 2017
DOI: 10.18609/cgti.2017.005
Citation: Cell Gene Therapy Insights 2017;3(1), 33-41.
Open access

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