Portal Bio's March 2026 newsletter is live, featuring five new experimental datasets across immune cell engineering, live-cell drug discovery assays, and high-throughput automated screening. Each experiment demonstrates a workflow that conventional electroporation and lipid nanoparticle methods cannot reliably replicate in primary immune cells.

March 2026 Research Highlights

CAR-T Cell Engineering Directly from Whole Blood

Mechanoporation delivered two circular RNA payloads simultaneously, encoding a CD19 CAR and membrane-bound IL-2, directly into T cells within unfractionated whole blood, with no upstream cell isolation or processing. Boosted samples achieved 52+% double-positive expression (CD19 CAR+ and IL-2+) compared to unboosted controls, while red blood cells and platelets remained unaffected. Read more here.

Enhancing Lentiviral Transduction in Primary B Cells

CD19+ B cells isolated from PBMCs are notoriously resistant to lentiviral transduction. By using mechanoporation to pre-deliver a circular RNA encoding a transduction enhancer, lentiviral GFP transduction reached 47% in boosted cells versus 13% in unboosted controls, a 3.6-fold increase. This demonstrates mechanoporation as a complement to existing viral workflows, extending lentiviral delivery to cell types that have historically been difficult to transduce. Read more here.

Intracellular Protein Detection in Live Cells via Antibody Delivery

Four antibodies were delivered simultaneously into live Ramos B cells and primary B cells to detect phosphorylated BTK (p-BTK) using a Lumit luminescence readout, with no cell lysis required. Portal-enabled live-cell detection achieved luminescence comparable to lysate-based assays, with a 7.3-fold signal induction in stimulated cells versus 4.5-fold for lysate, preserving native cellular context throughout. Read more here.

High-Throughput CRISPR Editing of Unstimulated T Cells

B2M-targeting CRISPR RNPs were delivered into unstimulated primary T cells using a Galaxy-i cartridge integrated into the Nnano Certus Flex liquid handler in 96-well plate format. Across nearly 100 automated dispenses, the system achieved 74% B2M knockout, 80% dextran-positive delivery, and 72% viability at Day 3. Read more here.

High-Throughput mRNA Screening in Primary Immune Cells

Twenty-seven distinct GFP mRNA constructs were screened in a single automated run using Galaxy-i and the Certus Flex platform, with PBMCs dispensed directly into pre-loaded 96-well plates. GFP expression varied substantially across constructs, with the top performer reaching ~700 MFI, enabling rapid ranking of mRNA construct performance in primary immune cells from a single plate run. Read more here.