Transduction efficiency is a critical determinant of CAR T-cell manufacturing quality. Analysis of 204 clinical CAR T-cell products revealed that transduction efficiency is shaped primarily by manufacturing workflows and protocol-dependent starting material composition. Higher transduction efficiency was associated with early memory-like cellular states, providing insights into optimizing CAR T-cell.

He and colleagues developed a transient, non-gene-editing platform for off-the-shelf allogeneic TCR-T therapy. By conferring tacrolimus resistance characteristics to IL-2/4/7 expanded TCR-T cells that display reduced alloreactivity, He et al. provided a proof-of-concept for an allogeneic TCR-T therapy approach that addresses both manufacturability, and unwanted graft and host alloreactivity concerns.

Zhang and colleagues engineered the poly(A) tail as a programmable regulatory element, showing that embedding cell-type-specific microRNA target sites directly within it confers robust, position-dependent silencing in off-target tissues while preserving activity in target cells. This strategy offers a new modular tool to enhance mRNA therapeutic safety and precision.

Tang and colleagues systematically review the structural biology, synthetic engineering, and immunological consequences of the mRNA 5' cap. By analyzing how Cap-0 through Cap-2 methylation patterns differentially affect translation and immune recognition, this work highlights the conceptual advances and translational potential of cap engineering for next-generation vaccines.

(Molecular Therapy 31, 1596–1614; June 2023)

Yuan and colleagues demonstrate that inhaled biodegradable nanosilica activates an alveolar macrophage–NK axis, triggering an IL-12/15/18 triad that programs memory-like NK cells. This non-fibrotic, cell-free strategy suppresses melanoma growth, prevents postsurgical recurrence, and synergizes with anti-PD-1, establishing a robust framework for in vivo NK cell immunotherapy.

The authors develop AminiCRoff, a compact dAsCas12f1-based epigenetic silencer compatible with single-AAV delivery. AminiCRoff mediates durable, heritable gene silencing comparable to the larger CRISPRoff and represses endogenous MYC to inhibit tumor cell proliferation, providing a versatile platform for in vivo epigenome editing.

(Molecular Therapy 31, 344–361; February 2023)

A vasoactive intestinal peptide (VIP)-based protein carrier self-assembles with respiratory syncytial virus circular RNA vaccines for intranasal delivery, inducing systemic antibodies, mucosal IgA, and Th1-biased protection in mice. This platform offers a protein-guided strategy for respiratory mucosal RNA vaccination and broadens the application of VIP in vaccine delivery.

This study developed a multi-layer inducible RNA switch that achieves transient expression of gene-delivery vectors in hepatic and non-hepatic tissues. As an exemplary application, this RNA switch triggers pulsive expression of gene editors that reduces the off-target effects and immunotoxicity of gene editing.

In preclinical studies, UB-VV400, an off-the-shelf, investigational lentiviral drug product, generates fully human anti-CD22 CAR T cells in vivo without the need for lymphodepletion. Activation of the synthetic rapamycin-activated cytokine receptor drives selective CAR T cell expansion and enrichment, resulting in complete tumor clearance and B cell depletion.

In the infection courses of different SARS-CoV-2 variants, disease outcomes and signatures were delineated by physiological changes, viral load, pathology, and pulmonary transcriptome analysis. This multi-dimensional landscape of disease outcomes and underlying mechanisms might provide important clues for immunotherapy of SARS-CoV-2 infection and pneumonia caused by other respiratory viruses.

MNK1 acts as a structural shield on MYH9, preventing YAP1-mediated platelet activation. Developing MD2 to lock this MNK1-MYH9 complex introduces a safe antithrombotic strategy, shifting the therapeutic paradigm from kinase inhibition to stabilizing protein-protein interactions against immunothrombosis.

By fusing MCM5, a subunit of the eukaryotic MCM2–7 helicase complex, to the N terminus of spCas9 (MCCas), the MCCas fusion protein enhances large-size fragment knockin via homologous recombination, reduces insertions and deletions (indels), and enables efficient large-size fragment insertions in human cells and rabbit embryos.

Latent HIV reservoirs evade both antiviral therapy and immune surveillance. Luo and colleagues develop a multifunctional fusion protein that couples reservoir reactivation with targeted immune engagement and clearance, offering a coordinated strategy to expose and eliminate persistent HIV-infected cells.

AAV-WM04, an AAV vector identified through in-vivo-directed screening in the adult cochlea, enables highly efficient and selective inner hair cell transduction. Dual-AAV delivery of OTOF using AAV-WM04 restores hearing in a DFNA9 deafness mouse model at low doses, highlighting its translational potential for gene therapy.

Nature Biomedical Engineering, Published online: 09 September 2026; doi:10.1038/s41551-026-01790-9A generative protein design workflow addresses important challenges with de novo protein engineering of chimaeric antigen receptors (CARs) to improve targeting of proteins important in cancer and create more effective CAR T therapies.

Nature Biomedical Engineering, Published online: 07 September 2026; doi:10.1038/s41551-026-01794-5Author Correction: A base editor for the long-term restoration of auditory function in mice with recessive profound deafness

Nature Biomedical Engineering, Published online: 31 August 2026; doi:10.1038/s41551-026-01782-9A protein engineering strategy enables nitric oxide-triggered reactivation of proteins using genetically encoded caged amino acids, allowing inflammation-localized control of protein activity, viral gene delivery and biosensing in vivo.

Nature Biomedical Engineering, Published online: 31 August 2026; doi:10.1038/s41551-026-01779-4This large-scale study of white matter structural connectivity during development reveals biomarkers associated with attention deficit hyperactivity disorder in youth that track symptom trajectories and predict differential treatment response.