Designing Next-Generation Chromatographic Resins for Biomanufacturing

Within biomanufacturing, sorptive separations are the workhorse for purifying protein therapeutics, vaccines, and cell & gene therapy products. The chemical diversity of chromatographic, membrane, and filtration ligands has been largely limited to simplistic single-mode interactions (e.g., charge or hydrophobic). To create more efficient separations, a new class of “multi-modal” ligands has been introduced which contains chemical moieties synergistically interacting through charge, hydrophobicity, and hydrogen bonding. The commercial multimodal materials, however, span a narrow chemical space and recent findings have shown that they often lack orthogonal interaction behaviors. Using chemically diverse immobilized peptide and peptide-mimetic libraries, our group focuses on dramatically expanding the chemical search space for developing the next generation of multimodal ligands. We create new bioseparation materials with the goals of i.) de-bottlenecking downstream purification through dramatic improvements in chromatographic throughput, capacity, and efficiency, ii.) developing optimized orthogonal multimodal materials that operate synergistically, and iii.) designing new materials that selectively remove problematic impurities that impact product stability, shelf life, safety, and efficacy. Additionally, we apply discovery platforms to enable efficient and platformable purification solutions for emerging classes of therapeutics.

Designing Tunable Drug Delivery Vehicles

Nanoparticle systems loaded with therapeutic payloads have received significant attention as drug delivery vehicles thanks to their ability to deliver a cargo throughout the body at high doses. Considerable efforts have focused on designing intelligent systems with chemically functionalized moieties to engineer important behaviors such as preferential tissue targeting, improved pharmacokinetic properties, and improved tissue penetration. Nanoparticle systems functionalized with peptides offer an exciting opportunity to take advantage of established discovery techniques, such as phage display, to discover peptides that bind specific targets (i.e., tumors). Unfortunately, these biology-based peptide discovery techniques are largely limited to incorporation of only the 20 naturally amino acids, which are susceptible to degradation and rapid clearance in vivo. Using synthetic, non-natural peptide libraries created directly on nanoparticles, our group is developing in vivo techniques for directly discovering nanoparticle systems with desired properties including controllable pharmacokinetics and tissue-specific targeting.

Undergraduate Researchers

We are always looking for enthusiastic undergraduate students that are interested in doing research!

If you are interested in joining our group, please contact Professor Vecchiarello with your CV at qzv7pp@virginia.edu