Cell Article Details Safe and Effective DNA/RNA Delivery via Proteolipid Vehicles

Entos Pharmaceuticals, a clinical-stage genetic medicines company based in Edmonton, has recently published a groundbreaking research article in the journal Cell. The study, titled "Safe and Effective Delivery of DNA and RNA Using Proteolipid Vehicles," introduces a novel delivery platform for nucleic acid medicines that aims to transcend the limitations of existing delivery systems.

The new platform, known as FAST-PLV, integrates fusion-associated small transmembrane (FAST) proteins into a proteo-lipid vehicle. This innovative system is capable of efficiently delivering mRNA or plasmid DNA into a diverse array of cells and tissues, exhibiting low immunogenicity and widespread distribution throughout the body. The research, spearheaded by Entos, was a collaborative effort involving the University of Alberta, Dalhousie University, Oisín Biotechnologies, and Aegis Life, Inc.

Dr. John Lewis, the senior author of the study and CEO of Entos Pharmaceuticals, highlighted the significance of this breakthrough. Traditional delivery platforms such as adeno-associated viruses (AAV) and lipid nanoparticles (LNP) have made substantial advancements in genetic medicine, leading to approved therapies and vaccines for various severe diseases. However, these platforms still have significant limitations. The FAST-PLV platform has been designed to address these gaps, enhancing the potential of genetic medicines that patients urgently require.

The FAST-PLV technology represents a fusion-powered delivery system that combines viral and non-viral approaches, enabling a novel mechanism for the intracellular delivery of RNA and DNA. Unlike AAV and LNP, which rely on endocytosis, the FAST protein allows the PLV to directly fuse with the plasma membrane of target cells. This significantly enhances the potency and tolerability of genetic medicines and allows for the development of formulations that are not liver-centric. This enables the therapeutic doses of nucleic acid therapies to reach cells and tissues throughout the body.

The efficacy, safety, and biodistribution of the FAST-PLV platform were evaluated through various animal model studies. The results indicated that the platform is non-immunogenic, which supports the possibility of repeated dosing of genetic medicines, a crucial factor for many therapeutic applications.

Dr. Arun Raturi, the senior author and Chief Scientific Officer of Entos Pharmaceuticals, expressed pride in the advancements achieved with the FAST-PLV platform. He emphasized that this innovation not only showcases the potential to overcome current gene delivery limitations but also reflects their commitment to developing safer and more effective therapies. The publication of this research in Cell marks a pivotal milestone and heralds a new era in genetic medicine.

The FAST-PLV platform is the cornerstone of Entos' Fusogenix™ PLV™ delivery system. Entos Pharmaceuticals is leveraging this technology to develop treatments for various conditions, including congenital generalized lipodystrophy, obesity, Stargardt disease, and cystic fibrosis, in addition to their VAX-002 vaccine program. The company is also exploring applications in the central and peripheral nervous systems, oncology, and longevity, among other areas, in collaboration with its partners.

Entos Pharmaceuticals was established in 2016 and has been dedicated to advancing genetic medicines through its proprietary Fusogenix PLV system. This platform utilizes FAST proteins to facilitate the direct fusion of nucleic acid with target cells. Collaborations with global companies like Eli Lilly have accelerated the impact of their platform. Entos Pharmaceuticals is headquartered in Edmonton, Canada, with subsidiaries in San Diego, California, and London, United Kingdom.

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