Reviews & Analysis

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.

Quadruplet codons allow multiplexing of non-canonical amino acids within single polypeptides in living cells. We show that including high-usage triplet codons after quadruplet codons can improve their decoding efficiency in genetic circuits, which allowed us to develop a system for the programmable biosynthesis of exotic macrocyclic peptides in cells.

Satellite cells, the stem cells of skeletal muscle, are responsible for muscle development and regeneration. Although low in abundance, satellite cells can be isolated from muscle but cannot be propagated successfully in culture in numbers needed for therapeutic use. We developed a method to generate cells with satellite cell characteristics from skeletal muscle organoid cultures.

A method using retron recombineering for phage genome modification may facilitate access to therapeutic phages.

Two CRISPR tools harness DNA-dependent polymerases for genome editing — and may overcome some limitations of prime editors.

The therapeutic principle of allogeneic hematopoietic cell transplantation, one the most common forms of cancer immunotherapy, is alloreactivity, yet its molecular determinants remain largely unknown. An analytical framework now enables personalized assessment of alloreactivity from whole-exome sequencing of donor–recipient pairs, to help with prognostication of disease relapse and immune-mediated complications.

We have discovered an effect, termed stacking-induced intermolecular charge transfer-enhanced Raman scattering (SICTERS), that enhances the Raman signal intensities of small molecules by relying on their self-stacking rather than external substrates. This effect enables the design of substrate-free small-molecule probes for high-resolution, non-invasive transdermal Raman imaging of lymphatic drainage and microvessels.