Overview
Nvelop Therapeutics has stepped into the spotlight as a promising $100-million startup, addressing a critical issue in gene therapy: the effective delivery of genetic medicines. This challenge isn’t new, but Nvelop, armed with substantial seed funding, is tackling it head-on with two innovative, in vivo delivery platforms. These platforms have been developed by renowned gene editing experts David R. Liu and J. Keith Joung.
Innovative Platforms
One of the key approaches from Liu’s lab involves engineered DNA-free virus-like particles (eVLPs). These assemblies of viral proteins infect cells but lack viral genetic material, thus negating many concerns related to traditional viral vectors. Liu’s paper in Cell in 2022 highlights the eVLP platform’s capability to deliver therapeutic ribonucleoproteins (RNPs) both in vitro and in vivo. This platform boasts advantages such as minimal off-target effects while enhancing the safety of prime editing. Liu’s prime editor eVLPs aim to restore protein expression and even rescue partial visual functions in models of genetic blindness, as reported in Nature Biotechnology.
Similarly, Joung’s lab has been pioneering the creation of enhanced VLPs. These VLPs incorporate virally-derived glycoproteins outside their membrane, bearing a cargo molecule inside. They represent a step forward from earlier VLP technologies. Joung’s research also includes the development of human-derived VLPs, utilizing human endogenous retrovirus (HERV)-derived envelope proteins. These human envelope proteins enhance the potential for immune tolerance and redosability, which could be crucial for successive therapeutic applications.
Key Figures
Nvelop is helmed by key figures like CEO Jeff Walsh and CSO Melissa Bonner. Walsh has emphasized the crucial role of solving in vivo delivery challenges for broader applications in cell and gene therapy. Bonner, with nearly a decade of experience at bluebird, underscores the strides Nvelop has made in scalable manufacturing. Bonner notes the progress in producing material at a scale significant enough to test clinical applicability.
Both Liu and Joung have substantial academic and research credentials. Liu serves as a professor and director at the Broad Institute and is a Howard Hughes Medical Institute investigator. Joung, who previously held a notable chair at Massachusetts General Hospital, now focuses on applying his knowledge to real-world therapeutic scenarios through Arena BioWorks.
Combined Efforts
The components from Liu’s and Joung’s labs offer potential for modularity. Nvelop aims to blend these platforms to refine and optimize genetic cargo delivery. The company values the modularity of these technologies, considering it a significant advantage for future applications.
Liu and Joung aren’t the only pioneering figures in the field. Other notable researchers like Jennifer Doudna and Feng Zhang are developing their unique platforms. Doudna’s team at UC Berkeley has been working on enveloped delivery vehicles (EDVs) for precise genome editing. Meanwhile, Zhang’s efforts at the Broad Institute have led to the foundation of Aera Therapeutics, focusing on genetically-based medicines using protein nanoparticle (PNP) delivery systems.
Delivery Technologies
When considering delivery technologies, it’s pertinent to analyze the advantages and limitations of existing systems. For instance:
| Delivery Method | Advantages | Limitations |
|---|---|---|
| Lentiviral Vectors | Infects dividing and non-dividing cells | Potential oncogenic integration, immune response |
| Adeno-Associated Viruses (AAV) | High specific tissue targeting | Limited packaging size, potential for immune response |
| eVLPs | Safe, minimal off-target effects | Still under optimization for clinical use |
| Human-Derived VLPs | Improved immune tolerance, redosability | Early-stage development, scalability |
Each method provides a different approach to delivering genetic cargo. The key lies in balancing effectiveness, safety, and scalability.
Leadership and Investors
The leadership at Nvelop represents a blend of scientific prowess and industry experience. Alongside Jeff Walsh and Melissa Bonner, the company benefits from the wisdom of experienced figures such as Lisa McGrath, the Chief People Officer, who brings a wealth of expertise in biotech HR management.
Nvelop’s growth and development are supported by partnerships with various venture capital firms. Firms like NewPath Partners, Atlas Venture, and GV have backed Nvelop, ensuring robust financial and strategic support. These collaborations are central to advancing Nvelop’s cutting-edge platforms and pipeline of therapeutics.
Scalable Manufacturing
One of the pivotal achievements at Nvelop is the scalability of their technologies. This aspect addresses one of the major bottlenecks in gene therapy: producing therapeutic agents at a scale suitable for widespread clinical use. Bonner highlights the importance of this manufacturing capability, noting it as essential for transitioning from laboratory research to real-world medical applications.
Impact on Gene Therapies
The implications of Nvelop’s platforms on gene therapies and genetic medicines are profound. The ability to deliver genetic cargo efficiently and safely to specific cell types is a game-changer for treating various conditions, including undruggable diseases. Effective in vivo delivery systems could revolutionize the treatment landscape by enabling precise, programmable, and targeted therapies.
Future Prospects and Collaborations
Nvelop continues to explore new avenues and collaborations to refine and expand their platforms. With ongoing research and partnerships with leading academic institutions and life science investors, the company looks poised to make significant strides in the field of gene and cell therapy. The potential for impactful clinical applications remains high as they continue to optimize their delivery technologies and expand their therapeutic pipeline.
Researchers like Liu, Joung, and their contemporaries drive the field forward, tackling in vivo delivery challenges head-on. Their collective efforts could reshape our understanding and application of genetic medicines, opening new doors to treat previously untreatable conditions with innovative, safe, and efficient delivery mechanisms.
