Delivering the Promise of Gene Therapy

Gene therapy holds the potential to cure genetic disorders by directly correcting underlying genetic defects. However, the delivery of genetic therapeutics to target specific cell types remains a challenge. Traditional adeno-associated viruses (AAVs) and lipid nanoparticles (LNPs) have been the primary carriers for gene therapies. AAVs, while effective, have limitations such as small payload capacity, potential for immunogenicity, and complex manufacturing processes that hinder scalability and cost-effectiveness. LNPs, popularized by their use in mRNA COVID-19 vaccines, also face challenges, including immunogenicity, limited payload diversity, and difficulty with cell targeting as well.

The Potential of PNPs

Battelle has developed a platform for the discovery of novel polymeric nanoparticles (PNPs) delivery vehicles. Battelle uses polymer chemistry to design PNPs with tailored properties that offer advantages over traditional gene carriers: they can encapsulate larger and multiple types of genetic material, are less immunogenic and toxic, and can be tailored to target specific cells, reducing both off-target effects and the required dose for efficacy.

Additionally, PNPs can be manufactured cost-effectively at scale due to the simplicity of their synthetic processes.

At the heart of this advancement is Battelle’s HIT SCAN™ platform, which applies the design-build-test-learn approach to nanoparticle development. The platform begins with automated polymer synthesis, allowing for the creation of a diverse library of PNPs. These nanoparticles are then subjected to high-throughput in vitro and in vivo screening, assessing characteristics like cargo compatibility, delivery efficiency, biodistribution, and cytotoxicity. The data collected is used to refine the nanoparticles through machine learning algorithms, enhancing their design based on performance metrics.

Science in Action

Battelle applied this technology in a collaborative effort with UC Davis and the Pennington Biomedical Research Center at the University of Alabama, Birmingham. These institutions utilized PNPs developed via the HIT SCAN™ platform to target Schwann cells for the treatment of Neurofibromatosis (NF1), a genetic condition characterized by tumor growth along nerves. Early results indicate successful targeting and delivery of a large genetic payload, showcasing the platform’s ability to rapidly iterate and improve nanoparticle designs based on biological feedback.

Delivering Better Drugs to Patients, Faster

The HIT SCAN™ platform represents a significant advancement over current technologies. It not only addresses key limitations of AAVs and LNPs but also demonstrates feasibility through its streamlined synthesis process. Its ability to rapidly produce a wide array of targeted, effective, and safe nanoparticles at a reduced cost is a game-changer for the field of gene therapy.

There are >500 gene therapies in the pipeline with U.S. gene therapy healthcare expenditures projected at ~$25B by 2026. The translation of these therapies to the market will require new delivery solutions, and Battelle’s HIT SCAN platform will increase success rate and speed of approval of these therapies by solving the delivery challenges upfront.

This innovative approach pushes the boundaries of nanoparticle technology and significantly enables the practical delivery of gene therapies, marking a pivotal step forward in personalized medicine.