Revolutionary nonviral vectors offer safer and more affordable gene delivery
The precision genetics medicine company Mediphage has developed an innovative DNA ministrings platform for safe, effective, and accessible ex vivo (cell) and in vivo (gene) therapies, including chimeric antigen receptor T-cells (CAR-Ts), CRISPR/Cas, and pluripotent stem-cell therapeutic applications.
Gene and cell therapies hold great potential for the treatment of a wide range of chronic disor- ders. But the costs remain astronomical, ranging from $400,000 to $1 million per treatment. These high costs are largely due to the use and production of expensive vectors to deliver DNA to cells. Approximately three-quarters of the more than 2,000 current gene therapy trials use viral vectors owing to their unrivaled efficacy. However, the safety risks of insertional mutagenesis and immunogenicity continue to take lives.
In addition, these therapies can only be applied once, and, because they cannot be titrated or personalized to a patient’s needs, are not capable of curing disease. Moreover, they are difficult to maintain, scale, and store, contributing to a backlog of up to 1.5 years in the industry. Effective and safer nonviral approaches are in high demand.
Mediphage Bioceuticals is a precision genetics medicine company with a mission to eradicate suffering from a wide range of chronic diseases through revolutionary therapeutics. The Toronto-based company, formed in December 2015 as a spin-off from the University of Waterloo, uses bacteriophage elements to generate safe, effective, and accessible phage- based therapeutics.
Mediphage’s DNA ministrings (msDNA) are efficient, customizable, and redosable nonviral vectors for ex vivo and in vivo cell or gene therapies, and lymphocyte (B-cell and T-cell), stem cell, and gene- editing therapeutic applications (Fig. 1). msDNA is capable of expressing a multigene cassette of interest safely and affordably, without compromising efficacy or efficiency of production. This innovative technology confers an unrivaled safety profile, while also being similarly efficacious and less expensive than any comparable technologies.
“msDNA is the safest, most scalable and effective solution to cell and gene therapy vectors,” said Roderick Slavcev, Mediphage’s founder and CEO. “With the highest safety profile across viral and non- viral vectors, DNA ministrings enhance the transition of current genetic engineering technology into true personalized genetic medicine.”
Fig. 1 | Transforming genetic medicine. Linear covalently closed (stable) double stranded DNA ministrings (msDNA) are efficient, customizable, and redosable nonviral vectors for use within personalized cell or genetic medicine, including lymphocyte (B-cell and T-cell), stem cell, and gene-editing therapeutic applications.
Safe and scalable
Unlike conventional vectors, the msDNA platform consists of linear covalently closed (stable) strings, making it the safest tool for therapeutic DNA delivery. These unique vectors have no immunostimulatory components and are the only vector type capable of protecting against potentially harmful or mutational vector insertions into the chromosome by selectively providing a kill switch upon undesired chromosomal integration. msDNA also outperforms other DNA vectors, with an increased rate of cellular uptake that is up to eight fold higher.
msDNA is generated within only 8 hours via a patented Escherichia coli in vivo production system, which is highly scalable and requires only simple temperature shifts to generate large-scale quantities. Milligrams of msDNA can be produced in a single day, significantly lowering production costs and maximizing accessibility.
To date, msDNA in vitro validation has been completed, with the results published in the Nature and Cell journals. Mediphage is now conducting next-stage safety and efficacy studies and is manufacturing msDNA in compliance with current good manufacturing practice (cGMP) regulations. The US Patent and Trademark Office has issued a patent for the msDNA platform and production and a continuation-in-part patent for gene-editing applications such as CRISPR/Cas and for enhanced production. Moreover, the company is pursuing in-house oncology and dementia therapeutic development, with a provisional patent already in place for a phage- display breast cancer vaccine and another platform patent on the horizon.
Unlocking vast potential
Currently, msDNA is being evaluated by therapeutic development partners using gene therapy, chimeric antigen receptor T-cells, DNA vaccines, induced pluripotent stem cells, CRISPR, and B-cell immuno- therapy approaches, as well as recombinant adeno- associated virus production, across a variety of applications. Mediphage’s customers consist of small to large biopharma companies interested in the use of more desirable gene or cell delivery approaches.
Using a hybrid business model strategy, Mediphage outlicenses the msDNA platform to cell and gene therapy companies across various therapeutic indications. This approach allows Mediphage to validate its msDNA technology in these areas while developing a second-generation targeted msDNA platform. With each licensee, Mediphage carries out a 3 to 6-month evaluation phase, issuing a material transfer agreement, and produces msDNA for each licensee. Following successful testing, Mediphage enters a licensing agreement to produce custom- ized msDNA. Agreements include service, royalty, and milestone fees, and all revenue generated supports in-house research and development of the second-generation targeted msDNA platform and future therapeutics.
Mediphage is now seeking additional partners interested in evaluating msDNA for a broad range of therapeutic applications. “Only msDNA can meet any genetic need, and as a naturalized biologic, can serve as personalized genetic medicine,” Slavcev says. “As the global cell and gene therapy market size continues to increase at an anticipated compound annual growth rate of 50%, our elegant gene-delivery vector platform holds tremendous promise for unlocking the vast and growing potential of personalized genetic medicine in the treatment of a myriad of chronic diseases.”
Roderick Slavcev, Founder and CEO
Toronto, Ontario, Canada
Tel: +1-647-243-5200 ext. 3402