Pioneers of Promise: Top 40 in Gene Delivery

Even as numerous gene therapies clear regulatory hurdles, one obstacle continues to cast a shadow over progress: delivery. Here we present our non-viral delivery report that identifies top-40 emerging early-stage companies and covers the current landscape, including the various modalities under development.

• AAV remains the vector of choice in most in vivo gene therapy applications, used in >80% of the >2,000 gene therapies currently under development.
• LNPs dominate the non-viral delivery segment, piggybacking on the successful use of such technologies by Moderna and Pfizer/BioNTech during the coronavirus pandemic.
• Phase III studies by Intellia Therapeutics of liver-targeting mRNA-LNPs have commenced, cementing the company’s position as the leading player in the non-viral gene editing space.
• Ex-liver delivery remains a core challenge for in vivo applications of mRNA-LNPs — only one non-liver tissue, lung, has observed clinical advancements (Arcturus Therapeutics & ReCode Therapeutics — Phase I for CF).
• Non-viral vectors are evolving beyond lipid- and polymer-based systems, with key opinion leaders backing virus-like particles (VLPs) as a modality with significant potential.
• Non-viral delivery companies strike large biopharma deals, as evidenced by GenEdit’s recent $644M deal with Genentech to develop polymer nanoparticles for autoimmune indications.
• VC activity remains high, with top biotech investors participating in large financing rounds of Capstan Therapeutics ($175m series B — LNPs) and Nvelop Therapeutics ($100M seed — VLPs).
• Significant academic breakthroughs were made in 2023, including the first reports of efficient delivery to photoreceptors and hematopoietic stem cells by LNPs in vivo.

DALL·E 3: Lipid nanoparticle delivering RNA to a cell.