This SBIR Phase I project will address the need for a product that can dramatically increase the recovery and purification speed for viral vectors used in gene therapy. Seven thousand rare diseases that have few or no treatment options are affecting 10% of the US population. Although gene therapies are promising for the treatment of many rare diseases, most are at an early stage of development and face challenges for the large- scale production of gene delivery vectors. Technologies like the one proposed will contribute to improving human health by enabling the rapid and scalable purification of lentiviral vectors (LVs), which are among the fastest growing delivery vectors used in gene therapy. Conventional methods to purify LVs involve a large number of steps and achieve low overall yields of ~20-30%. The goal of this SBIR Phase I project is to demonstrate the feasibility of developing affinity membrane chromatography columns that rapidly purify LVs from vector cell supernatant with high recovery and infectivity compared to conventional approaches. Products derived from this innovation will be first-in-market, disposable membrane chromatography columns that can simplify the LV purification process and improve the overall yield to ~60-70%. Purilogics expects these products will have a major impact on gene therapy development and commercialization by greatly improving the yield of this important type of delivery vector.
The aims of the Phase I study are (i) to synthesize and characterize affinity membranes and (2) to test prototype membrane columns for capture purification of viral vectors.
In Specific Aim 1, we will evaluate the roles played by synthesis conditions and membrane pore size on performance using in-house screening experiments. We will test the hypothesis that the unique combination of our proprietary ligand with high affinity for the envelope surface glycoprotein on LVs, a high surface area support membrane, and Purilogics' proprietary membrane fabrication method will yield products with high LV binding capacity. Mild elution conditions will be developed that lead to high recovery of active LVs.
In Specific Aim 2, Purilogics will collaborate with researchers at Clemson University to evaluate membrane performance for purification of LVs prepared using a commercial cell line. Multiple iterations of synthesis and performance characterization will improve membrane performance. In Phase II, Purilogics plans to (i) establish a scalable process to produce prototypes for comprehensive performance testing, determining sterilization protocols, product shelf life, and reusability; and (ii) conduct field research with industrial partners who are potential customers. Market entry for the new column products will be sales to purification scientists and engineers in biopharmaceutical companies. These individuals are end-users, influencers and decision makers. The estimated total addressable market for prepacked, disposable capture-step chromatography columns under development by Purilogics is expected to reach $450M by 2029.
Gene therapy is one of the most promising therapeutic modalities to treat and cure diseases with limited or no alternative treatment options. Lentiviral vectors are emerging as one of the favored gene-delivery vehicles in clinical trials. The goal of this SBIR Phase I project is to develop an affinity membrane chromatography product for the rapid purification and efficient recovery of lentiviral vectors from vector cell supernatant. These products will contribute to improving human health by enabling scalable production of the vectors that are needed for this emerging field of medicine.
