Bringing you the latest cutting-edge research and commentary in bioscience.

Cell & Gene Therapy Insights

Cell & Gene Therapy Insights

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Journal

Welcome to the latest issue of Cell and Gene Therapy Insights – the open access, peer-reviewed publication that brings you the latest insight and commentary from leading experts from academia and industry.

Editorial
Commercial Insights
Interview

Next steps in targeting the CNS with AAV-driven gene therapy

Spotlight Article

Interview

Bruce Goldsmith

Trends and advances in gene therapy delivery and gene editing

BRUCE GOLDSMITH is Passage Bio’s CEO and President, and he also serves on its Board of Directors. Dr Goldsmith has extensive experience in the biopharma and biotechnology industries through the many roles he has held across the research and corporate spectrum. Prior to Passage, Dr Goldsmith was a Venture Partner at Deerfield Ventures and Interim CEO of Civetta Therapeutics.

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A return to rational capsid design? Predicting the future of AAV vector R&D

Spotlight Article

Interview

R. Jude Samulski

Trends and advances in gene therapy delivery and gene editing

R JUDE SAMULSKI received his PhD in Medical Microbiology and Immunology from the University of Florida. His graduate work (1978–82) involved the cloning of the adeno-associated virus (AAV) genome and the demonstration of AAV as a viral vector, including the first US patent involving non-AAV genes inserted into AAV. During his post-doctoral training at Princeton, he developed the AAV 2 ITR vector backbone, commonly used by most labs today as well as the initial establishment of an AAV production system. At the University of Pittsburgh Department of Biology, he was the first to demonstrate AAV transduction in rodent brain and muscle that culminated in the first clinical trials in the brain (Canavan) and muscle (DMD). In 1993, he was hired at the University of North Carolina (UNC) to establish a Gene Therapy Center. For over 25 years, Dr Samulski, as a Professor of Pharmacology and the Director of the Gene Therapy Center at UNC, has led a team of multiple Principal Investigators developing novel viral vectors and clinical gene therapy programs. He was recognized in 2008 by the American Society of Gene & Cell Therapy (ASGCT) as the first recipient of the Outstanding Achievement Award, was awarded the National Hemophilia Foundation’s Investigator of the Year in 1999 and was the first non-MD to be placed on the University of Florida’s Wall of Fame. He has served as past President of ASGCT and was invited to China to meet with the Chinese Minister of Health and soon after was recognized as one of China’s Thousand Points of Light, a recognition bestowed on individuals whose contributions are benefiting mankind. In addition to being the lead inventor on over 300 patents in the field of AAV vectors and gene therapy, he is a scientific founder of ASGCT, Merlin, Asklepios BioPharmaceutical, NanoCor Therapeutics, Chatham Therapeutics, Bamboo Therapeutics, Viralgen, and other entities that continue to advance the field of human gene therapy and was selected as a seminal speaker at the Royal Society of Science in London in the Isaac Newton Lecture room on ‘Delivering novel therapeutic in the 21st century’ (October 24, 2018).

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Precise and non-disruptive gene editing based on programmable nickases

Spotlight Article

Interview

Trends and advances in gene therapy delivery and gene editing

MANUEL GONÇALVES is a molecular biologist focusing on the development of gene delivery and gene editing systems. After a post-graduation period in a gene therapy company, Dr Manuel Gonçalves was awarded a fellowship from the Portuguese Foundation for Science and Technology to perform his PhD research on the investigation of hybrid viral vector systems for the stable genetic modification of human cells. In 2015, Dr Gonçalves became associate professor at the Department of Cell and Chemical Biology of the Leiden University Medical Center. In this capacity, he supervises a team whose research interests are converting viral vectors into delivery agents of gene-editing tools, studying the impact of epigenetic mechanisms on the performance of different gene-editing tools and strategies, and improving gene-editing approaches by guiding specific DNA repair pathways after introducing into target cells programmable nucleases or ‘nickases’. In this context, his team has pioneered the investigation of viral vectors as delivery vehicles of TALENs and CRISPR-Cas9 nucleases.

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An educated approach: AI-enabled neoantigen vaccine R&D

Interview

Roman Yelensky

Trends and advances in gene therapy delivery and gene editing


INNOVATION INSIGHTS


ROMAN YELENSKY is Gritstone Oncology’s first employee and serves as chief technology officer, with responsibility for the EDGE tumor antigen identification platform. Previously, Dr Yelensky was vice president at Foundation Medicine, which he joined at its inception. At Foundation Medicine, he co-led sequence data analysis for FoundationOne and led validation studies supporting clinical laboratory accreditation and testing of more than 100,000 patients. Dr Yelensky established Foundation Medicine’s FDA-regulated products program, leading to FDA approval of the first NGS-based companion diagnostic. He holds a PhD in bioinformatics and genomics from the Massachusetts Institute of Technology and has co-authored more than 75 manuscripts, including most recently on EDGE in Nature Biotechnology.

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Gene editing as a key enabler of allogeneic cell therapy

Spotlight Article

Interview

Torsten Meissner

Trends and advances in gene therapy delivery and gene editing

TORSTEN MEISSNER obtained his PhD in biology at Free University, Berlin and moved on to do postdoctoral research in immunology and stem cell research at Dana-Farber Cancer Institute and Harvard University in Cambridge, Massachusetts. Torsten is currently an Instructor in the Department of Surgery at Beth Israel Deaconess Medical Center in Boston, a Harvard Medical School affiliated research hospital. His research combines genome, cell, and tissue engineering with the overall goal to take down the immune barrier to transplantation. Torsten is currently developing methods to generate immune-silent, living blood vessels from human induced pluripotent stem cells (iPSC) that can be used for disease modeling and vascular reconstruction.

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Expert Insight

High dose systemic gene therapy: emerging trends on safety and efficacy

Spotlight Article

Expert Insight

Ying Kai Chan, Hansell H Stedman, Roland W Herzog, Guangping Gao & George M Church

Trends and advances in gene therapy delivery and gene editing

Systemic delivery of adeno-associated viral (AAV) vectors has traditionally been used in the clinic for liver-directed programs such as hemophilia A and hemophilia B. With the approval of Zolgensma® for the treatment of spinal muscular atrophy type I (SMA1), high dose systemic gene therapy has become a promising approach for systemic and neuromuscular transduction for various indications. Here, we discuss emerging findings on safety and efficacy from recent clinical trials utilizing high dose systemic gene therapy. In particular, we highlight previously unappreciated observations related to safety, and discuss possible causes and future directions.

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Polymer nanoparticles: potential for efficient, biodegradable, and cost-effective delivery of gene therapy to multiple tissues

Spotlight Article

Expert Insight

Timothy C Fong, Steven Bodovitz & Kunwoo Lee

Trends and advances in gene therapy delivery and gene editing

The field of gene therapy has had a resurgence of interest and activity in the last few years due to recent approvals and development of new gene editing technologies. Recent approvals include Luxturna®, which uses adeno-associated virus (AAV) to deliver DNA to treat inherited retinal disease and Onpattro®, which uses a lipid nanoparticle (LNP) to deliver RNA interference (RNAi) to treat hereditary transthyretin-mediated amyloidosis. New technologies that are starting to reach human testing include CRISPR-Cas9, CRISPR-Cas12a and various base editors, but the bottleneck is delivery. AAV is the most widely used viral platform for in vivo delivery, but it has significant limitations, including delivery of only nucleic acids, small payload capacity, potential for integration, pre-existing and acquired immunogenicity, and cost of manufacturing. LNPs are also limited to nucleic acid payloads and have not shown efficient in vivo delivery outside of liver and muscle. A new polymer-based nanoparticle system is being developed that has the potential to overcome these limitations and enable the next generation of gene therapy.

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Innovator Insight

FectoVIR®-AAV: a giant step for AAV large scale manufacturing

Spotlight Article

Innovator Insight

Alengo Nyamay’antu, Malik Hellal, Mathieu Porte & Patrick Erbacher

Trends and advances in gene therapy delivery and gene editing

The number of advanced therapy medicinal products (ATMPs) to treat inherited genetic disorders is in constant growth, with a global 32% increase in new clinical trials in the last 4 years. ATMPs have demonstrated their success with already more than ten approved for commercialization. The success of AAV as the most promising viral vector for gene therapy is due to low immunogenicity, broad tropism and non-integrating properties. One major challenge for translation of promising research to clinical development is the manufacture of sufficient quantities of AAV. Transient transfection of suspension cells is the most commonly used production platform, as it offers significant flexibility for cell and gene therapy development. However, this method shows some limitations in large scale bioreactors: inadequate transfection protocol, reduced transfection efficiency and lower productivity. To address this concern, we present data on the novel transfection reagent FectoVIR®-AAV specifically developed to bring flexibility of transient transfection together with scalability and speed to market.

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Exosomes at scale as next-generation cell free medicines: fact and fiction

Innovator Insight

Ian Dixon

Trends and advances in gene therapy delivery and gene editing


INNOVATION INSIGHTS


In 2020, exosomes (also known as extracellular vesicles [EVs]) are emerging from academic laboratories and into biotechnology company led clinical trials. But this progress has, until now, been held back by the absence of a robust, scalable and proprietary purification technology. Despite this, a handful of biotechnology companies are promoting their manufacturing capabilities and progress into clinical trials. This article considers the fundamental question behind claims of scalability of EV manufacturing and its implications for the development of this promising therapeutic modality.

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