Journal Archive

Editorial

Clinical translation of viral vectors for gene therapies and beyond

Spotlight Article

Editorial

Challenges & advances in Viral vectorS

Gerhard Bauer and Mohamed Abou-El-Enein

Gene therapy has, after years of setbacks, returned as a highly advantageous novel therapy for the treatment of severely debilitating diseases for which there were no treatment options. As marketed therapeutic products, gene therapies will add an arsenal of new options to provide life-saving clinical benefits to many patients worldwide.

DOI: 10.18609/cgti.2016.064
Citation: Cell Gene Therapy Insights 2016; 2(5), 507-511.

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AAV vector and gene therapy: en route for the American dream?

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Editorial

Challenges & advances in Viral vectorS

Nathalie Clément

Nathalie-Clement

Over the past 2 years, AAV has been propelled to the front of the line as one of the most efficient, robust, reliable and safe bio-tools to mediate long-term gene expression in human patients with genetic diseases, thanks to key advancements, both at the clinical and technical levels.

DOI: 10.18609/cgti.2016.066
Citation: Cell Gene Therapy Insights 2016; 2(5), 513-519.

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Review

AAV vector production: state of the art developments and remaining challenges

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Review

Otto-Wilhelm Merten

Challenges and Advances in Viral Vectors

In 2012, an adeno-associated virus (AAV) vector reached the market following its approval by the European Medicines Agency for the treatment of patients with lipoprotein lipase deficiency. This marketing authorisation represented an important step for the gene therapy field, moving from exploratory towards routine clinical use. However, a number of challenges remain in the production and manufacture of these therapies. In principle, four different production platforms (HEK293[T] transfection, stable packaging/producer cell lines, herpes simplex virus system and baculovirus system) have been developed and for some, scale-up to a 2000 L scale has already been performed. Despite these achievements and the well-advanced technological developments in manufacturing technology, further improvements in AAV technology are required to increase vector titers, and improve vector quality and potency. This article provides a review of the four vector production platforms, recent improvements and developments as well as perspectives on future requirements.

Submitted for review: Oct 10 2016 Published: Dec 1 2016
DOI: 10.18609/cgti.2016.067
Citation: Cell Gene Therapy Insights 2016;2(5), 521-551.
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Expert Insight

Advances and challenges in the use of recombinant AAV vectors for human gene therapy

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Expert Insight

Arun Srivastava

Challenges and Advances in Viral Vectors

Recombinant vectors based on a non-pathogenic parvovirus, the adeno-associated virus (AAV), have taken center stage in the past decade. The well-established safety of AAV vectors in 162 Phase I/II clinical trials (and one recent Phase III trial) in humans to date, as well as their clinical efficacy in several human diseases, are now well documented. Despite these remarkable achievements, it is becoming increasingly clear that the full potential of AAV vectors composed of the naturally occurring capsids is unlikely to be realized. In this Expert Insight article, I will describe the advances that have been made, and the challenges that remain, in the optimal use of AAV vectors in human gene therapy applications. I will also attempt to provide additional avenues of research and development that could be pursued in order to further ensure both safety and efficacy of AAV vectors in targeting a wide variety of human diseases, both genetic and acquired, in the not-too-distant future.

Submitted for review: Oct 10 2016 Published: Dec 1 2016
DOI: 10.18609/cgti.2016.061
Citation: Cell Gene Therapy Insights 2016;2(5),553-575.
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Continuous flow centrifugation: importance in vector scale up

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Innovator Insight

Challenges and Advances in Viral Vectors

Sandra Meriño & Scott Glanzman

sandra-headshot-100x120scott-glanman-120x100

Sandra Meriño has been the Global Project Director at Alfa Wassermann Separation Technologies group for 16 years managing process support, product installation and validation including PQ testing. Previously worked at Medeva (now Seqirus) in the UK as a downstream processing scientist working on traditional and recombinant viral and bacterial vaccine scale up and scale down. Holding a BSc Hons in Biological sciences and Biochemistry form Manchester University.

Scott Glanzman is the Director of Marketing for Alfa Wassermann Separation Technologies and holds a Bachelor of Science in Education from Indiana University. Beginning over 36 years ago in secondary education, he applied that experience to a career that lead to senior positions in sales and marketing at companies that included McKesson Medical-Surgical, ThermoFisher, and Roche Diagnostics.

DOI: 10.18609/cgti.2016.069
Citation: Cell Gene Therapy Insights 2016; 2(5),577-582.

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Mouse mammary tumor virus-based vector for efficient & safe transgene delivery into mitotic & non-mitotic cells

Spotlight Article

Expert Insight

Stanislav Indik

Challenges and Advances in Viral Vectors

Retroviruses are cellular parasites that have evolved to deliver and integrate their nucleic acids to the host chromosomes. Therefore, they have been converted into gene delivery vehicles (vectors) and used for the effective transduction of genes in tissue culture cells as well, as for therapeutic gene transfer approaches. Until recently, vectors derived from mouse mammary tumor virus (MMTV) were inefficient in gene delivery. However, recent advances in betaretrovirology revealed the underlying obstacles that prevented the conversion of MMTV to an efficient gene delivery vehicle and allowed the construction of a high-titer MMTV-based vector system with a split genome design. The vector combines several desirable properties of retroviral vectors such as random integration into the host chromosomes and the capability to transduce genes into non-dividing cells. This article will discuss the latest developments and the remaining challenges in utilizing MMTV-based vectors in gene delivery.

Submitted for review: Oct 10 2016 Published: Dec 1 2016
DOI: 10.18609/cgti.2016.062
Citation: Cell Gene Therapy Insights 2016;2(5), 589-598.

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State of the art lentiviral vector manufacturing

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Interview

Challenges and Advances in Viral Vectors

Dr Chetan Tailor

Chetan-Tailor

Dr Chetan (Chet) Tailor is the Founder and Director of Tailored Genes. He has over 20 years of experience in molecular biology, cell culture and generating retrovirus/lentivirus vectors. Dr. Tailor obtained his Ph.D in the field of Virology from the University of London UK in 1995, under the supervision of Prof. Robin A. Weiss and Prof. Mary K. Collins, two of the top Scientists in the field of retroviruses/lentiviruses and gene therapy. He then spent 5 years (1996-2001) as a post-doctoral Fellow at the Oregon Health Sciences University in Portland, Oregon, USA under the supervision of Prof. David Kabat. Dr Tailor next established his own research laboratory at The Hospital for Sick Children Research Institute, Toronto, Canada from 2001-2012. From 2012-2014, Dr Tailor was Scientific Director of the Vector Core Facility at the University Health Network, Toronto, Canada generating custom-made lentivirus vectors for Canadian and US customers before finding Tailored Genes.

DOI: 10.18609/cgti.2016.068
Citation: Cell Gene Therapy Insights 2016; 2(5), 583-588.

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Repurposing lentiviral vectors for delivery of genome editing tool kits

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Expert Insight

Jacob Giehm Mikkelsen

Challenges and Advances in Viral Vectors

Viruses are natural carriers of genetic information and enzymes that operate in infected cells. For years, gene therapists have exploited the gene-carrying capacity of virus-derived vectors, and lentiviral vectors based on HIV-1 have become key tools in biomedical research and genetic therapies. Inspired by the capability of the virus to package and transport its own enzymatic tools for reverse transcription and integration, we and others have engineered lentiviral particles incorporating and delivering foreign hitch-hiking proteins. Here, I describe attempts to repurpose lentiviral vectors for delivery of genome editing tool kits. Administration of protein by lentiviral particles results in effective and short-lived protein activity in virus-treated cells even with low concentrations of protein, supporting further development of virus-based protein delivery strategies for safe genome editing applications.

Submitted for review: Oct 15 2016 Published: Dec 1 2016
DOI: 10.18609/cgti.2016.063
Citation: Cell Gene Therapy Insights 2016;2(5), 599-614.

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Foamy virus: an emerging viral vector for human gene therapy

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Interview

Challenges and Advances in Viral Vectors

Dr Jennifer E. Adair

Jennifer-Adair

Dr Jennifer E. Adair received her Bachelor of Science degree from Youngstown State University and her Doctor of Philosophy degree from Washington State University. She is currently an Assistant Member in the Clinical Research Division at Fred Hutchinson Cancer Research Center and a Research Assistant Professor in the School of Medicine at the University of Washington in Seattle. Her laboratory develops and translates gene therapy using hematopoietic stem cells as a treatment for genetic, malignant and infectious diseases. Specifically, her lab has translated successful drug resistance gene therapy to protect blood from otherwise myelotoxic chemotherapy used to treat solid tumors, functionally corrective gene therapy for Fanconi Anemia, X-linked severe combined immunodeficiency syndrome and Wiskott-Aldrich syndrome, and anti-HIV gene therapy in combination with drug resistance gene therapy for the treatment of AIDS-lymphoma. The lessons learned from these studies provide research directives to overcome remaining barriers to mainstream clinical application of hematopoietic stem cell gene therapy.

DOI: 10.18609/cgti.2016.065
Citation: Cell Gene Therapy Insights 2016; 2(5), 615-622.
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Alpharetroviral self-inactivating vectors: an emerging tool for gene therapy

Spotlight Article

Interview

Challenges and Advances in Viral Vectors

Dr Axel Schambach

Axel

Dr Axel Schambach is Acting Director of the Institute of Experimental Hematology at Hannover Medical School. He completed his medical training at the University of Hamburg, with international electives carried out at USCF, Baylor University and the Children’s Hospital Zurich. In 2005 Axel gained his PhD from the Institute of Experimental Hematology, Hannover Medical School, focusing on enhanced transgene expression of retroviral vectors by post-transcriptional elements. In 2013 he became Professor for Gene Modification of Somatic Cells at Hannover Medical School and Acting Director of the Institute of Experimental Hematology. Axel is also a Visiting Scientist and Lecturer at Boston Children’s Hospital. He is lead author on a number of scientific papers, has received multiple awards including the ESGCT Young Investigator Award in 2010 and is lead on a patent for alpharetroviral SIN vector system.

DOI: 10.18609/cgti.2016.070
Citation: Cell Gene Therapy Insights 2016; 2(5), 623-627.

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