Journal Archive

Interview

Addressing the Limitations of AAV Vectors through Evolutionary Guided Vector Design

Spotlight Article

Interview

LUK H VANDENBERGHE

Anc-80: latest updates on the novel Anc-AAV gene therapy vector

Luk Vandenberghe

LUK H VANDENBERGHE, PHD, is an Assistant Professor at Harvard Medical School and Associate Member of the Broad Institute of Harvard and MIT in Boston, MA, USA. He directs the Grousbeck Gene Therapy Center at Massachusetts Eye and Ear Infirmary in Boston, USA, a part of the Ocular Genomics Institute, a bench to bedside research program to study, diagnose, and develop treatments for diseases of the eye. His previous work led to the discovery of novel AAV serotypes such as AAV9, novel insights into AAV structure-function, and vector immunobiology. His laboratory at Harvard addresses mechanistic questions on AAV virology, develops technologies aiming to overcome hurdles to gene therapy clinical applications, and actively translates gene therapy programs in hearing and vision. His research focuses on delivery questions, specifically on the adeno-associated virus (AAV) for therapeutic gene delivery. Recent studies leverage structural and evolutionary information on AAV as a starting point for the design of synthetic viral vector systems, a first generation of which is referred to as AncAAVs which are now progressing to the clinic for a number of indications. Dr. Vandenberghe previously co-founded GenSight Biologics and Akouos. He also is a founder, board member, and advisor to Odylia Therapeutics, a non-profit catalyzing translation for gene therapies within the challenging field of ultra-rare disorders. Dr. Vandenberghe has over 50 peer reviewed publications and more than a dozen licensed patents, mostly related to gene therapy methods, technologies, and applications.

Published: 18 October 2018
DOI: 10.18609/cgti.2018.056
Citation: Cell Gene Therapy Insights 2018; 4(S1), 573-579
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Meeting the Demand: Next-Generation Viral Vectors for Gene Therapy

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Interview

Ryan Scanlon

Anc-80: latest updates on the novel Anc-AAV gene therapy vector

Ryan Scanlon Lonza

RYAN SCANLON has been the commercial leader for Lonza’s viral gene therapy business since 2013, where he has been instrumental in shaping Lonza’s gene therapy strategy by driving the business case for the recent relocation and expansion of the new Lonza Houston site. His current focus at Lonza includes commercial development and partnering activities for the next generation Ancestral AAV (Anc-AAV) technology which Lonza exclusively in-licensed from Mass. Eye & Ear and the lab of Dr Luk Vandenberghe, Harvard Medical School. Prior to his time in the gene therapy sector, Ryan served as the Head of Business Development for the Lonza Microbial Development Services business since 2009 where he performed strategic planning and led the launch of several new services and proprietary technologies. He joined Lonza in 2007 as Associate Director of Marketing & Intelligence for the Custom Manufacturing business where his analysis of the gene therapy market supported the case to acquire Vivante GMP Solutions (now Lonza Houston). Ryan has a BSc in Biochemistry from the College of Engineering and Applied Science at Lehigh University.

Published: 18 October 2018
DOI: 10.18609/cgti.2018.060

Citation: Cell Gene Therapy Insights 2018; 4(S1), 627-636
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Flexible, Modular Manufacturing to Address Viral Vector Capacity Bottlenecks

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Interview

Anc-80: latest updates on the novel Anc-AAV gene therapy vectoR

Xin Swanson

XIN SWANSON serves as the Commercial Development Lead for Lonza’s Viral Vector Gene Therapy Business. She has over 20 years of experience in the Pharma/Biotech industry, developing viral gene therapies and monoclonal antibody therapeutics. Over the course of her career, Xin has held various positions in R&D, Process Development and Commercial Development functions. She has been with Lonza for more than 10 years and has played an instrumental role in the growth of Cell and Gene Therapy business. Xin holds a PhD in Biochemistry from Texas A&M University and an MBA degree.

DOI: 10.18609/cgti.2018.079

Citation: Cell Gene Therapy Insights 2018; 4(S1), 771-775.
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Innovator Insight

Establishment of a scalable manufacturing platform for in-silico-derived ancestral adeno-associated virus vectors

Spotlight Article

RESEARCH ARTICLE

Anc-80: latest updates on the novel Anc-AAV gene therapy vectoR

Bingnan Gu, Vijetha Bhat, Wenling Dong, Hai Pham, Stephanie Pubill, Nagarjun Kasaraneni, Eric Onishi, Francesca Vitelli & Anandita Seth

Adeno-associated virus (AAV) is an effective viral vector for gene therapy due to its non-pathogenicity, high transduction efficiency, broad tissue specificity and long-term transgene expression activity. As such, AAV has become a vector of choice with over 120 active clinical trials worldwide. With this increased demand also comes the need for scalable GMP manufacturing processes that are robust and can support large-scale production. However, current manufacturing of AAV vectors for gene therapy is labor-intensive, resulting in high production costs (adherent-based process) or taking much longer to establish (e.g., producer cell line). Here we report the establishment of a scalable manufacturing platform for AAV production based on transient triple transfection of suspension HEK293 cells. Through flow cytometry, limiting dilution and productivity screening, we first isolated a high producer clonal suspension HEK293 cell line. After medium selection and transfection optimization, we scaled up the production process to 50-Liter using single use bioreactors (SUB). The platform was initially developed for a novel AAV vector (Anc80), that belongs to a large family of novel AncAAV’s, as described previously by Luk Vandenberghe [1] but has also been used for the successful production of other AAV serotypes. Using affinity chromatography followed by ion exchange chromatography, we successfully purified the recombinant AAV/Anc80 products with a high percentage of full viral particles. Taken together, we have established an effective, cost-efficient and scalable manufacturing process for AAV/Anc80 that supports the ever-growing production demands in the AAV gene therapy market.

Submitted for review: Aug 29 2018 Published: Oct 16 2018
DOI: 10.18609/cgti.2018.078
Citation: Cell Gene Therapy Insights 4(S1) 753-769.
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