Journal Archive

Editorial

Treating Alzheimer’s disease with stem cells: how far have we come?

Editorial

Kaylene M Young and Solène Ferreira

Solene FerreiraKaylene_Young

In 2015, 46.8 million people worldwide have been diagnosed with dementia. This figure is predicted to rise to 131.5 million people by 2050 [1]. Alzheimer’s disease (AD) is the leading cause of dementia, and can be further divided into familial AD, which results from genetic mutation and has an early age of onset, and sporadic AD. Sporadic AD is by far the most prevalent form, and over the past decade numerous risk factors have been linked to its development. Aging is still the most significant risk factor, with more than 1 in 20 people over the age of 60 developing the disease. AD is characterized by the deposition of β-amyloid in the form of plaques, the aggregation of hyper-phosphorylated tau as intracellular neurofibrillary tangles, neuron loss, and brain atrophy. Many of the pathological features of AD were identified over a century ago, however new mechanisms driving the pathology are still being uncovered today [2].

DOI: 10.18609/cgti.2015.029
Citation: Cell Gene Therapy Insights 2015; 1(2), 133-137. Open access

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Commercial Insights

Commercial Insight – November 2015

Alan Boyd, Mark Curtis & Rahul Sarugaser

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.

GENE THERAPY:

The majority of the news around gene therapy this month has related to financing and the question of whether the IPO window is still open in the USA? Wave and Voyager got their IPOs away, with Wave achieving the share price they wanted, whilst Voyager had to cut back a bit. Unfortunately GenSight Biologics from Paris, has pulled its IPO in New York. Getting an IPO away at the moment looks difficult but only time will tell and it will be interesting to see what happens in the New Year.

CELL THERAPY:

Japan has shown an insatiable thirst for all things regenerative medicine. This was compounded by recent revisions, in November 2014, to the Pharmaceutical Affairs Law that introduced a conditional approval pathway for regenerative medicine products that allows for their development and marketing in only a few years. While the Japanese pharmaceutical market is one of the largest in the world, the country has lagged its peers in the commercialization of regenerative medicine products by a significant margin. Two notable regenerative medicine acquisitions were posted this year by Japanese companies; the first was Fujifilm’s acquisition of Cellular Dynamics International, a company founded in 2004 by stem cell biologist James Thomson that carved itself a niche in the manufacture of research-grade cells. The second, which came to light this past month, is Astellas’ plans to acquire Ocata Therapeutics (formerly Advanced Cell Technology), a company focused on regenerative ophthalmology, for $379 million.

DOI: 10.18609/cgti.2015.026
Citation: Cell Gene Therapy Insights 2015; 1(2), 139-149.Open access

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Clinical Trial Insights

Clinical Trial Insight: Cell and Gene therapy – December 2015

Dr Alexey Bersenev, Yale University, USA, providing an expert overview of the most important clinical trials, cases and cohort studies conducted in academic and industry with particular focus on later-stage efficacy data.
DOI: 10.18609/cgti.2015.027 Citation: Cell Gene Therapy Insights 2015; 1(2), 151-155.

Age related macular degenerationPositive Phase 3 data from Spark Therapeutics

In October, US-based gene therapy company Spark Therapeutics reported positive data from their Phase 3 pivotal trial in inherited retinal dystrophies [1]. 31 subjects were randomized and assigned to intervention versus control at a ratio of 21:10. The primary endpoint of the study – vision improvement – was met, with a large difference compared with control. However, one of secondary endpoints, visual acuity, was not met. Spark’s results are remarkable, because this is the first success in a Phase 3 gene therapy trial under US Food and Drug Administration (FDA) jurisdiction. Based on the results of this trial, Spark is planning to file a Biologic License Application with the FDA to marketing their gene therapy in USA.

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Interview

Prof. Carl June: Unlocking the potential of T-cell therapies

Video Interview

Prof. Carl June is the Richard W. Vague Professor in Immunotherapy in the Department of Pathology and Laboratory Medicine. He is currently Director of Translational Research at the Abramson Cancer Center at the University of Pennsylvania and is an Investigator of the Abramson Family Cancer Research Institute. He is a graduate of the Naval Academy in Annapolis, and Baylor College of Medicine in Houston 1979. He maintains a research laboratory that studies various mechanisms of lymphocyte activation that relate to immune tolerance and adoptive immunotherapy for cancer and chronic infection. He has published more than 300 articles and is the recipient of numerous prizes and honors, including election to the Institute of Medicine and the American Academy of Arts and Sciences.

DOI: 10.18609/cgti.2015.025
Citation: Cell Gene Therapy Insights 2015; 1(2), 157-162. Open access

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Perspective

Moving from passive to rescue design packaging: helping cells arrive alive with smart shippers

Expert Perspective

Kevin O’Donnell

The packaging of time- and temperature-sensitive healthcare products has changed very little over the past quarter century. However, the advent of new, fragile cell therapies demands the need for greater temperature precision, and the ability to collect multiple data of environmental and handling conditions within the distribution environment through continuous real-time monitoring and on-line accessibility. This article explores the lessons learned from the decade-long tortuous path taken by the pharmaceutical and biopharmaceutical industries with regard to shipping environmentally fragile products and how it has led to the development of rescue design packaging capable of precision performance with flexible intervening capabilities during transit – so-called “smart” shipping containers. Embedded electronics provide monitoring and recording a host of data on a per-package basis. The data is managed through a proprietary and secure web-based application where the tracking, management and analytics of each package can be applied in a multitude of ways, from gaining greater understanding of a products’ stability in the distribution environment to choosing the best routes and modes of transport.

Revised article submitted: Sept 29 2015 Published: Nov 2 2015
DOI: 10.18609/cgti.2015.016
Citation: Cell Gene Therapy Insights 2015; 1(2), 163-171.Open access

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Review

MSC homing & immunomodulatory properties in cancer therapies: searching for the perfect balance

Review

Sofia Lourenco, Elizabeth F Maughan & Sam M Janes

Mesenchymal stem cells are non-hematopoietic adult stem cells with multi-lineage potential. Their inherent tumor tropism and easy isolation, expansion and transduction, make them attractive vehicles for the delivery of anti-cancer agents. Mesenchymal stem cell tumor homing is still poorly understood and a wide variety of factors have been reported to affect this complex process, with some inconsistencies. Their immunomodulatory properties have led to some caution towards their use in cancer patients but this field remains controversial, as both immunosuppressive and immune-enhancing phenotypes have been described and appear reversible as well as highly sensitive to the local microenvironment. This review will focus on mesenchymal stem cell homing and immunobiology in the context of cancer and the translational potential of these cells.

Submitted for Review: Oct 15 2015 Published: Dec 10 2015
DOI: 10.18609/cgti.2015.024
Citation: Cell Gene Therapy Insights 2015; 1(2), 173-192.Open access

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Spotlight on: Translation and application of gene editing

spotlight-header

Foreword: Translation and applications of gene editing

Chris Mason & Elisa Manzotti

The last 24 months have seen an explosion in genome engineering techniques that are revolutionizing our ability to edit specific elements of the genome across a multitude of organisms. The discovery of CRISPR/Cas9 in particular has unlocked a relatively simple and accessible way of manipulating DNA sequences and it is this ease of use that has led to a huge surge in the number of research publications utilizing this method.

DOI: 10.18609/cgti.2015.028
Citation: Cell Gene Therapy Insights 2015; 1(2), 193-194.Open access

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The promise of therapeutic genome engineering

Spotlight Article

Andrew Bassett

Translation and Application of Gene Editing

Recent advances in genome engineering have revolutionized our ability to specifically and delicately manipulate the genomes of essentially any organism including human cells, and have already led to more accurate cellular and animal models of disease. Such techniques also have the potential to permanently repair genetic mutations associated with human disease, many of which are currently difficult or impossible to treat by traditional means. This review discusses the technologies currently available for genome engineering, the strategies for their application in patients and current progress towards applying such techniques to specific diseases. I highlight the exciting avenues for such therapeutic genome engineering in the future and challenges to its successful application.

Submitted for Review: Aug 11 2015; Published: Dec 10 2015; DOI: 10.18609.cgti.2015.017
Citation: Cell Gene Therapy Insights 2015; 1(2), 195-214.Open access

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Expert Insight

Exciting developments in CRISPR/Cas9-mediated approaches for Duchenne MD

Spotlight Article

Marc Moore, Denis Vallese, George Dickson & Linda Popplewell

Translation & Application of Gene Editing

The first use of the prokaryotic clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system in mammalian cells a couple of years ago paved the way for a revolution in the field of genome engineering. The availability of this simple-to-design, easy-to-use and multiplexing RNA-guided system enabled its widespread use in various applications. This technology has opened new avenues for the investigation and potential treatment of genetic diseases, such as Duchenne Muscular Dystrophy (DMD). This Expert Insight describes how CRISPR/Cas9 research could potentially be used therapeutically in the treatment of DMD, along with the principal hurdles and difficulties faced with its use, and hypothesizes on potential novel targets/uses of CRISPR/Cas9 in relation to DMD.

Submitted for Review: Sep 29 2015 Published: Dec 10 2015 DOI: 10.18609/cgti.2015.022
Citation: Cell Gene Therapy Insights 2015; 1(2), 215-230
Open access

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Beta testing: preclinical genome editing in β-globin disorders

Spotlight Article

Carsten W Lederer & Marina Kleanthous

Translation and Application of Gene Editing

The β-globin disorders β-thalassemia and sickle cell disease have been at the forefront of gene therapy development from its very inception. Owing to their frequency, severity and exceptionally well characterized molecular pathology, and to the availability of hematopoietic stem and progenitor cells as substrate for therapies, these disorders promise both fast insights into new methodologies and eventual return on investment. Accordingly, β-globinopathies are also a favorite subject of the nascent field of genome editing and its most pioneering approaches to achieving therapeutic functional correction of gene expression. Be it by mutation-specific correction, modulation of disease modifiers or site-specific gene addition, genome editing of β-globinopathies has already delivered significant insights into the design of synthetic nucleases and the suitability of different correction strategies. This Expert Insight reviews recent progress in the application of gene-editing tools and different model systems towards the establishment of new therapies for β-globin disorders.

Submitted for review: Oct 5 2015 Published: Dec 10 2015 DOI: 10.18609/cgti.2015.021
Citation: Cell Gene Therapy Insights 2015; 1(2), 231-242Open access

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Stem cell-derived organoid cultures and genome editing tools

Spotlight Article

Amanda Andersson-Rolf & Bon-Kyoung Koo

Translation & Application of Gene Editing

The term stem cell was first used in the late 19th century to describe ‘the ancestor’ unicellular organism, the origin from which all multicellular organisms evolved. Our definition today is that of a cell characterized by two properties: self-renewal (the capacity to generate new stem cells) and multipotency (the ability to differentiate into different cell lineages) [1–4]. Due to these characteristics, stem cells hold great potential for clinical use by providing an unlimited source of cells for cell therapy in regenerative and/or personalized medicine. To realize this potential, the development of stem cell culture systems, as well as stem cell genome editing tools, has been of paramount importance. Here, recent advances in culture systems and genome editing tools will be discussed. This Expert Insight will provide an overview of current, state-of-the-art stem cell culture systems, with a focus on the recent progress in 3D tissue culture of both embryonic and adult stem cells, as well as the genome editing tools present today. Finally, we will discuss how stem cell and genome editing technologies can be combined to gain insights into human development and disease, and to fulfil the promises of stem cell research in the clinic.

Submitted for review: Aug 26 2015 Published: Dec 10 2015; DOI: 10.18609/cgti.2015.019
DOI: 10.18609/cgti.2015.022
Citation: Cell Gene Therapy Insights 2015; 1(2), 243-251
Open access

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Revolutionizing genome editing with CRISPR/Cas9: patent battles and human embryos

Spotlight Article

Hannah Smith-Willis & Beatriz San Martín

Translation and Application of Gene Editing

A new genome editing technology – the CRISPR/Cas9 system – promises to revolutionize the way we modify genetic material in living cells, including how we treat disease. The battle over who owns and controls the technology in this exciting new area is fierce, with numerous patents being filed in multiple jurisdictions. Concerns have, however, been raised over the use of the CRISPR genome editing technology following news in April this year that a team led by Dr Huang Jienjin in Guangzhou, China, had used the technique on human embryos. This article considers the patent landscape for CRISPR, focusing in particular on the two original applications that cover this technology and who may stake a claim over its ownership. It then explores what may be protectable as a patent in Europe in the context of genome editing of human embryos and what regulations are in place to control what might be done, not only by way of research, but also in the clinic, with a focus on the position in the UK.

Submitted: Oct 15 2015 Published: Dec 10 2015; DOI: 10.18609/cgti.2015.020
Citation: Cell Gene Therapy Insights 2015; 1(2), 253-262Open access

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Fyodor Urnov: The power & promise of ZFN-mediated genome editing

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Podcast Interview

Translation and Application of Gene Editing

Fyodor Urnov, PhD, is Project Leader and Senior Scientist at Sangamo BioSciences, Inc. where he co-developed human genome editing with engineered zinc finger nucleases (ZFNs). Dr Urnov previously led the company’s research and development efforts in deploying genome editing for crop trait engineering (in partnership with Dow Agrosciences) and in generation of engineered cell lines for manufacturing, improved generation of transgenic animals and as research reagents (in partnership with Sigma-Aldrich). In his current role as Project Leader for the Hemoglobinopathies, Dr Urnov heads Sangamo’s collaboration with Biogen to develop genome editing as a one time, lasting treatment for beta-thalassemia and sickle cell disease. Dr Urnov is also an associate adjunct professor in the department of Molecular and Cell Biology at the University of California, Berkeley. Dr Urnov received his PhD from Brown University and holds a BSc in Biology from Moscow State University. He is an author on more than 60 scientific publications and an inventor on more than 90 issued and pending US patents related to ZFN technology.

DOI: 10.18609/cgti.2015.023
Citation: Cell Gene Therapy Insights 2015; 1(2), 263-274. Open access

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