Portal Bio Awarded $8M DARPA Contract to Create Field Deployable Cell Therapy Production Systems
Portal Bio Awarded $8M DARPA Contract to Create Field Deployable Cell Therapy Production Systems
Research Scale
High-Throughput Screening
Clinical Manufacturing
Application | Traditional Approach | Key Issues | Avg Delay and Cost | Portal's Approach | Key Advantages |
|---|---|---|---|---|---|
DEL Screening | Cell-free biochemical or lysate screens | DNA tags cause impermeability; miss cellular context | 6–12 months; $500K–$1M MedChem before cell testing | Delivers DEL compounds into cytosol, enabling live-cell screening despite DNA barcode impermeability | Early biological de-risking; bypass MedChem for non-viable hits; immediate cellular testing |
Target Engagement | Cell lysates or permeabilized cells (CETSA, BRET, FRET) | Destroys native environment; impermeable tracers require lysis | 2–4 weeks per compound; limited to permeable probes | Delivers NanoBRET/CETSA reagents into intact cells, enabling real-time drug-target measurement | Real-time kinetics in intact cells; preserves target conformation and post-translational modifications |
PROTAC Discovery | Lysate-based assays; engineered lines; endpoint measurements | Miss temporal dynamics; cannot use primary cells; destroys degradation machinery | 4–8 weeks validation; $200K–$500K per candidate | Delivers LgBiT for intracellular HiBiT complementation, enabling real-time degradation monitoring | Live-cell kinetic profiling; test in primary cells; real-time pharmacology |
Macrocyclic or Linear Peptides | Limited to permeable peptides; low-efficiency endocytosis | 80% of chemical space inaccessible; modifications compromise activity | 12–18 months permeability optimization; frequent failures | Achieves ~80% delivery in HEK293 with linear dose-response, decoupling permeability from binding optimization | Access full peptide chemical space; optimize binding without permeability constraints |
Hit-to-Lead | Biochemical screen → MedChem → cell testing | MedChem investment before validation | ~1 year; $1M+ before cell validation | Enables direct-to-biology screening—test hits immediately in live cells before MedChem investment | Verify activity before MedChem; save time and money on non-viable scaffolds |
Phenotypic Screening | Engineered lines; electroporation causes dysfunction | Primary cells difficult to transfect; electroporation alters phenotypes | 3–6 months; limited to model lines | Delivers compounds into primary cells at HTS scale, preserving function in iPSCs, T cells, disease-relevant types | Disease-relevant primary cell screens; preserved phenotypes; efficient multiplex delivery; HTS compatible |
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Jong Chul Park, Howard Bernstein, Scott Loughhead, Ricardo Zwirtes, Julia
Jennings, Valeria Nicolini, Christian Klein, Laura Codarri Deak, Pablo Umana,
Christine Trumpfheller, Armon Sharei
Colin J. Raposo, Judith D. Cserny, Gloria Serena, Jonathan N. Chow, Patricia Cho, Hanyang Liu, David Kotler, Armon Sharei, Howard Bernstein, and Shinu John
Matthew G. Booty, Kelan A. Hlavaty, Adam Stockmann, Howard Bernstein, Armon Sharei, Scott M. Loughhead, Hendrik Knoetgen, Christine Trumpfheller, Pablo Umaña, Ulrich H. von Andrian, Klavs F. Jensen, Robert Langer, Jacques, Eritza Chong, Lucas Pomerance, John T. Gonzalez, Shirley Mao, Megan Heimann, LeeAnn Talarico, Miye K. Jonathan Chow, Tarek Abdeljawad, Harry An, Sophia Liu, Vicente-Suarez, Defne Yarar, Melissa Myint, Amy Merino, Olivia Pryor, Kelly Volk, Katarina Blagovic, Ildefonso, Disha Subramanya, Anita Venkitaraman, Christian Yee, Emrah Ilker Ozay, Carolyne Smith, Lina Tian, Edylle How