Portal accelerates growth with latest $9M round led by NFX, an expanded DARPA contract, and broad adoption!
Portal accelerates growth with latest $9M round led by NFX, an expanded DARPA contract, and broad adoption!
Engineer CAR Cells Without Viral Vectors
CAR Cell Therapy
Non-Viral CAR Delivery
Deliver circRNA or mRNA encoding CARs directly to the cytosol without viral vectors, eliminating insertional mutagenesis risk and reducing manufacturing complexity.
Multi-Cell Compatibility
Engineer T cells, NK cells, and macrophages with the same platform. Consistent delivery across all major CAR cell types with consistent results across cell types.
Clinical-Scale Manufacturing
The MilliBooster cartridge integrates with GMP systems (Fresenius Kabi Lovo, Rotea) to process over 1 billion cells per run with high mRNA expression at scale.
Multiplexed Engineering
Simultaneously deliver multiple cargos in a single pass. Portal has achieved high triple-positive delivery of CRISPR RNP, mRNA, and dextran to T cells in one step.
Non-Viral CAR Delivery
Deliver circRNA or mRNA encoding CARs directly to the cytosol without viral vectors, eliminating insertional mutagenesis risk and reducing manufacturing complexity.
Multi-Cell Compatibility
Engineer T cells, NK cells, and macrophages with the same platform. Consistent delivery across all major CAR cell types with consistent results across cell types.
Clinical-Scale Manufacturing
The MilliBooster cartridge integrates with GMP systems (Fresenius Kabi Lovo, Rotea) to process over 1 billion cells per run with high mRNA expression at scale.
Multiplexed Engineering
Simultaneously deliver multiple cargos in a single pass. Portal has achieved high triple-positive delivery of CRISPR RNP, mRNA, and dextran to T cells in one step.
Explore detailed protocols and data in our CAR cell engineering app notes.
Portal supports multiple CAR cell manufacturing approaches, from standard activated T cell workflows to rapid whole blood processing.
Workflow | Cell Type | Cargo | Key Result |
circRNA CAR-T | Activated T cells | circRNA (CD19 CAR + mbIL-12) | 75.9% dual-positive expression; >90% tumor cytotoxicity at 3:1 E:T |
Whole Blood CAR-T | T cells (unprocessed whole blood) | mRNA (CD19 CAR + mbIL-2) | 52.9% CAR+ IL-2+ T cells in <10 minutes; no preprocessing required |
CAR-NK | NK cells | mRNA or circRNA (CAR construct) | Consistent delivery with maintained NK cell viability and cytotoxic function |
Multiplexed CAR-T | Unstimulated T cells | CRISPR RNP + mRNA + dextran | 85.7% triple-positive delivery; 59% B2M knockout at clinical scale |
In collaboration with Massachusetts General Hospital, Portal has demonstrated simultaneous delivery of two circular RNAs encoding CD19 CAR and mbIL-12 to activated T cells. The resulting CAR-T cells achieved 75.9% dual-positive expression and >90% tumor cell killing at a 3:1 effector-to-target ratio, with viability maintained at >75%. circRNA offers extended protein expression compared to standard mRNA, providing a longer functional window without genomic integration.
Portal has demonstrated generation of multi-engineered CAR-T cells directly from unprocessed whole blood, achieving high CAR+ IL-2+ T cell expression in under 10 minutes without cell separation or activation. Economic modeling suggests this workflow could dramatically reduce per-dose costs, with roughly 90% cost savings that could widely improve access to CAR-T therapy for B-cell lymphoma patients.
Portal's MilliBooster cartridge has been validated at clinical scale with Fresenius Kabi's Lovo cell processing system, achieving 92–94% mRNA expression (consistent across research and clinical scale) and ~60% B2M knockout in T cells at an optimal Lovo flow rate of 40 mL/min. B2M editing efficiency was 50–60% across multiple timepoints (Day 4 and Day 7), maintained at 59–60% post-expansion at clinical scale.
Conventional Approaches
Viral vector manufacturing adds 6-12 months lead time and significant cost
Insertional mutagenesis risk with lentiviral and retroviral integration
Limited to single-construct delivery per viral vector
Electroporation causes 330+ misregulated genes and impaired cell expansion
Requires cell isolation, activation, and multi-day processing before engineering
Per-dose cost of approximately $95,780 limits patient access
Portal Mechanoporation
No viral vectors needed; deliver circRNA or mRNA directly to the cytosol
Zero misregulated genes at q<0.1 threshold; 16x better T cell expansion
Multiplex delivery of CAR + cytokines + gene edits in a single step
Engineer CAR cells from whole blood in under 10 minutes
Compatible with T cells, NK cells, and macrophages on the same platform
Projected ~90% cost reduction to approximately $10,000 per dose
Portal enables delivery of diverse cargo types to CAR cells, supporting both transient and permanent modifications.
circRNA
mRNA
CRISPR RNP
Cas9 Protein
siRNA
Plasmid DNA
Peptides
Antibodies
Small Molecules
Anil Narasimha, Sophia Hirsch, Darby Kreienberg, Andrew Larocque, Eleni Rogers, Zhihui Song, Xi Ai, James Vasta, Matthew Robers, Alec Barclay, Armon Sharei