Reviews & Analysis

DNA delivery using lipid nanoparticles results in severe toxicity in mice. However, we find that the incorporation of endogenous anti-inflammatory lipids into the lipid nanoparticles mitigates this toxicity and enables prolonged gene expression.

The mechanism of translation initiation in linear and circular mRNAs influences translation efficiency. Covalent attachment of an N⁷-methylguanosine (m⁷G) cap increases protein production from circular mRNAs in mice. Hybridization with capped endogenous RNAs also promotes protein production in cells, suggesting that this interaction might also occur between endogenous RNAs.

Visualizing RNA molecules in live cells remains a challenge, and existing methods require genetic manipulation or have limited resolution. Our study overcomes these limitations by using the programmable CRISPR–Csm tool to bind and track individual transcripts in their native state.

Adipocytes can be isolated, genetically manipulated, and then reimplanted. In this study, these properties were leveraged to engineer adipocytes that can outcompete tumors for essential metabolic resources. In mouse cancer models, these adipocytes suppressed tumor growth, demonstrating a novel cancer therapy termed adipose manipulation transplantation (AMT).

The performance of AAV gene-therapy vectors is studied in machine-perfused human livers — and the presence of fatty liver disease makes a difference.

Large-scale profiling of drug-induced metabolic changes have potential for improving drug development but remain challenging. We created a computational and experimental large-scale metabolic profiling framework that enabled us to map metabolic effects for 1,520 diverse drugs. This platform revealed new modes of action and potential therapeutic uses for already market-approved drugs.

A method for designing high-affinity, specific binders to peptide–MHC complexes may improve the next generation of antigen-specific T cell-based therapeutics.

Gene therapy in the lungs could treat a range of devastating illnesses, but lack of safe and efficient delivery has held back the field. Here, in silico screening of millions of lipid nanoparticles (LNPs) yielded several chemically novel and highly potent LNPs for pulmonary gene therapy.

Natural and engineered Cas12 and TnpB variants offer diverse applications in genome editing and diagnostics.

Proteolytic chimeras constructed from various bioactive modules can degrade either cytoplasmic or extracellular proteins, but their pharmacology faces challenges. Now, a protein degradation platform built with engineered platelets enables the targeted depletion of intracellular and extracellular proteins at hemorrhagic sites, addressing several limitations associated with proteolytic chimeras.

Recent clinical trials testing CAR T cells on solid tumors have yielded promising outcomes that can be enhanced with further CAR engineering.

Ancestral sequence reconstruction enables the identification and synthesis of ReChb, an ancient form of CRISPR–Cas12a with a highly versatile functionality. ReChb can target any nucleic acid, with minimal restrictions, making it a multipurpose tool for genome editing and genetic diagnostics.

We developed NeoDisc, a computational antigen discovery pipeline that integrates multi-omics data, including genomics, transcriptomics and mass spectrometry-based immunopeptidomics. NeoDisc accurately identifies and prioritizes tumor-specific antigens and designs personalized cancer vaccines. The pipeline reveals tumor heterogeneity and emphasizes defects in antigen presentation that might affect the success of cancer immunotherapy.

Two major advances in optical pooled screening improve substantially on sensitivity and robustness, expanding its applicability to a broader range of biological contexts.

Sample, financial and labor requirements are key barriers to scaling up high-content phenotypic discovery efforts. A broadly applicable method overcomes these challenges through experimental compression (by pooling various perturbations) and computational deconvolution (of their individual effects), empowering the use of phenotypic screening to advance therapeutic discovery.

A CRISPR-based assay both recognizes and amplifies target mRNA, achieving sub-attomolar sensitivity with single-nucleotide resolution. This method enables the detection of low-abundance mRNA in extracellular vesicles, providing clinically relevant information for precision oncology.

Escherichia coli engineered to display cytokines destroy hard-to-treat tumors by boosting the activity of local native and adoptive immune effector cells.

Redesigning mRNA with chemo-topological strategies improves its stability and translation efficiency, paving the way for more effective mRNA therapeutics.

λ exonuclease (λExo) binds 5′-phosphorylated single-stranded DNA (pDNA) at complementary regions on double-stranded DNA and DNA–RNA duplexes under ambient conditions without a PAM-like motif. In the presence of Mg²⁺, λExo then digests the pDNA into nucleotides.

A differentiation method informed by developmental biology converts human pluripotent stem cells to engraftable hematopoietic stem and progenitor cells without the use of transgenes.