The aim of MAGIC is to accelerate the development of gene therapies and genome editing for muscular dystrophies by creating advanced humanized muscle models and innovative approaches. The goal is to improve the lives of people living with muscular dystrophies. 

Each month, we gather partners from the MAGIC project to discuss aspects in relation to gene therapies. Readers will learn who the people behind the MAGIC Project are, why we are committed to advancing gene therapies, and how our roles in MAGIC are crucial for achieving better health outcomes for people living with muscular dystrophies. This time, we are speaking with Marie Fertin, Chief Technological Innovation Officer at VIVEbiotech. 

In brief words, please let us know who you are individually and on behalf of which project partner organization. 

My name is Marie Fertin, Chief Technological Innovation Officer at VIVEbiotech.  VIVEbiotech is a Contract Development and Manufacturing Organization (CDMO) fully specialized in lentiviral vectors. We are proud to be part of the MAGIC project consortium. Our expertise in virology and bioprocessing enables us to translate novel engineered lentiviral vectors from the initial stages to preclinical studies. We achieve this by using our well-established plug-and-play platform to produce these vectors on a large scale. 

Why are you participating in the MAGIC project? How can your perspectives complement the MAGIC project goal to accelerate the development of genetic therapies for muscular dystrophies? 

The MAGIC project aims to accelerate the development of novel treatments for muscular dystrophy. While adeno-associated virus (AAV) capsid engineering is common for specific tissue targeting in in vivo therapy, lentiviral vectors (LVV) have traditionally excelled in ex vivo applications due to their broad tropism (targeting ability) when VSVg-pseudotyped. However, at VIVEbiotech, we see a growing potential for LVV-based in vivo treatments.  

With eight in vivo programs currently running in preclinical and clinical trials, we are well-positioned in this advanced therapeutic field. We provide large-scale, cost-effective, scalable, clinical-grade vectors through our regulatory-approved ex vivo and in vivo manufacturing platform that can accommodate different pseudotyped lentiviral vectors. This makes us a great partner for the preclinical translation of innovative engineered LVVs to an industrial manufacturing platform. 

What have been the current challenges regarding the development of genetic therapies for muscular dystrophies for you? 

Lentiviral vectors have not been the top choice for advanced muscular dystrophy treatments. The main challenge was the lack of well-developed pseudotyping strategies to specifically target myocytes. This hindered the development of LVV-based programs for treating muscular genetic disorders, despite their ability to integrate at low multiplicities of infection (MOI) in a safe and permanent manner with therapeutic transgenes. 

However, within the innovative MAGIC project, a groundbreaking approach developed by Cincinnati Children’s Hospital utilizes muscle-specific fusogenes for LVV pseudotyping. This allows for a new in vivo lentivirus-based approach to treat muscular dystrophy. These vectors can deliver therapeutic genes to myocytes with high specificity and efficiency. 

What are the main outcomes (direct results) you expect from the project? 

Thanks to the high-level collaboration of key developers in the gene therapy field within the MAGIC consortium, muscular dystrophy treatment programs, including those based on LVV, will benefit from state-of-the-art technologies and tools to achieve unprecedented technological outcomes.  

The MAGIC consortium allows us to demonstrate that LVV-based therapies —already administered in vivo for several applications— can also be effective in delivering therapeutic genes for muscular dystrophy. Their high cargo capacity, absence of preexisting immunity in the general population, and stable transgene expression upon cell transduction could lead to groundbreaking advancements to address current limitations in gene therapy. 

What are the expected impacts on your organisation from participating in the project? 

Being part of MAGIC represents a significant opportunity for VIVEbiotech to engage in cutting-edge research, bridging the gap between academia and industry. Our experience has shown that such collaborations are highly effective in securing and translating early-stage gene therapy programs to industry standards. 

We hope that our expertise will unlock new lentivirus-based gene therapy programs, increasing the visibility of LVV for in vivo administration strategies, particularly for advanced therapies targeting muscular genetic disorders. 

Given VIVEbiotech’s position in this specific market, we anticipate strengthening our role as a CDMO for both ex vivo and in vivo applications. Our ability to support innovative programs will be showcased, solidifying our status as a world-class provider of clinical and commercial-grade lentiviral vectors.