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The safety and efficacy of ribonucleoproteins for genome editing can be enhanced by formulations of lipid nanoparticles optimized for enhanced stability, delivery efficiency and editing potency of the protein complexes.

Multiplexed orthogonal base editing systems introduce different point mutations at two loci simultaneously.

Leber congenital amaurosis is caused by mutations in RPE65 and leads to retinal degeneration in children. Here, the authors show that in vivo base editing can prolong the survival of cone photoreceptors and rescue their function in a mouse model of the disease.

In vivo gene editing hinges on identifying an ideal delivery vehicle from numerous candidates. Here, authors establish the GFP-on mouse model capable of translating successful adenine base editing to a fluorescent readout thus enabling the rapid evaluation of genome editing delivery vehicles.

Subretinal viral delivery, in mice, of an adenine base editor and a single-guide RNA targeting a nonsense mutation in the Rpe65 gene restores near-normal levels of retinal and visual functions.

Edited bacteria were stably maintained in mouse gut for at least 42 days following the delivery of a base editor using an engineered phage-derived particle to modify Escherichia coli colonizing the gut.

Here, the authors show that base editing of CD33 and gamma globin genes in HSPCs results in the long-term engraftment of dual edited cells along with HbF reactivation and GO resistance in mice and nonhuman primates.

Programmable, RNA-guided nucleases are diverse enzymes that have been repurposed for biotechnological applications. Here, the authors mine an extensive genome-resolved metagenomics database and identified uncharacterized families of RNA-guided, compact nucleases.

Analysis of samples from the asteroid Ryugu provide evidence of late fluid flow in a carbonaceous asteroid, indicating that such bodies may have retained two to three times more water than previously thought.

A continuously evolved adenine base editor is compatible with various Cas proteins and mediates efficient A•T-to-G•C base conversions at a wide variety of PAM sites.

Engineered variants of DNA base editors have reduced RNA off-target editing while retaining DNA on-target efficiency.

Current base editors cannot simultaneously edit multiple loci with base-pair level precision, hindering complex genotype generation. Here the authors describe optimized Cas12a gRNA array designs, enabling base-pair conversions at up to 15 loci and with reduced bystander editing rates in human cells.

Inactivating PPP2R1A mutations correlate with better survival after immune checkpoint blockade in patients with ovarian clear cell carcinoma, suggesting that targeting the phosphatase 2A (PP2A) pathway may represent an effective startegy for improving responses to immunotherapy.

Engineered cancer mutations are linked with phenotypes in a multiplexed single-cell technology.

A base editor that concurrently modifies both adenine and cytosine broadens the potential applications of base editing.

Determining which covalent binding events impact protein function is challenging. Now, a strategy has been reported that integrates base editing and chemical proteomics to infer the functionality of ligandable cysteines in cancer dependency proteins by quantifying the impact of their missense mutation on cancer cell proliferation.

Wider editing windows and different PAM requirements enable a broad set of genomic positions to be targeted with A and C base editors.

Primary angle-closure glaucoma is a leading cause of blindness. Here, the authors identify rare deleterious variants in UBOX5 as risk factors and implicate BIP ubiquitination as a potential disease mechanism.

Combined high-throughput protein engineering with machine learning to curate libraries of CRISPR genome-editing enzymes with distinct genome targeting properties is described.

Using short-read sequencing data, Evoracle reconstructs full-length genotypes and fitness during directed evolution experiments, and can identify low-frequency variants before they can be identified using consensus mutations.

A custom adenine base editor can edit the variant of the β-globin gene that causes sickle cell disease into a non-pathogenic variant in human and mouse cells, and transplantation of the edited cells rescues sickle cell disease in mice.

An antibody–drug conjugate that targets the pan-haematopoietic marker CD45 combined with transplanted stem cells engineered to be shielded from it can eradicate leukaemic cells while preserving haematopoiesis.

UM171 promotes corepressor degradation by acting as a molecular glue to induce KBTBD4–HDAC1/2 interactions with the help of inositol hexakisphosphate.

The Kuju volcanic area’s shallow magma margin features a low-amplitude reflection zone that allows pressurized fluids to migrate upward, causing diverse earthquake clusters with complex mechanisms, according to analysis of magma-related and hydrothermal structures in the Kuju volcanic area in Japan.

Sajti and colleagues identify TREM2 as a critical factor in myeloid cells in response to hyperoxia-induced lung injury in neonates, finding that TREM2 deficiency protects mice from bronchopulmonary dysplasia.

The authors uncover the roles and regulations of DNA polymerase κ (Polκ) during DNA damage bypass. In addition to a catalytic function across minor groove DNA lesions, Polκ stimulates Polζ-mediated extension past various DNA lesions.

The ability to genetically modify haematopoietic stem cells would allow the durable treatment of a diverse range of genetic disorders but gene delivery to the bone marrow has not been achieved. Here lipid nanoparticles that target and deliver mRNA to 14 unique cells within the bone marrow are presented.

Highly pathogenic avian influenza is an increasing global concern but its distribution in remote regions is not known. Here, the authors conduct an environmental influenza surveillance study in remote, uninhabited regions of the Global South by sampling fresh bird guano.

Random number generators (RNGs) are indispensable tools for information security. The authors derive a security proof for a quantum RNG based on parity-symmetric radioactive decay, which can be made as small as a few-square-millimeter chip and whose source has no need for power generation.

A new base editor enables the creation of C-to-G base changes in human cells.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Morrison et al. find that in T-cells, the palmitoyl acetyltransferase DHHC18 palmitoylates the v-SNARE VAMP7 at Cys183 and show that a mutant that cannot be palmitoylated fails to localise to Golgi and traffic to the immune synapse after T-cell receptor activation. This study highlights the importance of palmitoylation in T-cell signalling.

A proof-of-principle quantum key distribution experiment based on the round-robin differential phase shift protocol is demonstrated. Using a coherent wave-packet containing five pulses, the quantum keys were distributed over up to 30 km of fibre.

Plasma wakefield accelerators promise compact, affordable future particle accelerators, but require deposition of enormous energy into a small volume. Here, the authors measure and simulate how this energy transfers from the wake into surrounding plasma, a process that ultimately governs the accelerator’s repetition rate.

Studies in humans and mice show that myocardial infarction recruits monocytes to the brain’s thalamus, promoting sleep, which in turn restricts cardiac inflammation and sympathetic signalling and assists healing.

Quasicrystals lack translational symmetry but display rotational order. Whether antiferromagnetic order can exist in quasicrystals has been unclear. Now, long-range antiferromagnetic order is shown in the icosahedral quasicrystal Au₅₆In_28.5Eu_15.5.

The iPROBE platform accelerates the design and optimization of engineered biosynthetic pathways using a combination of cell-free protein synthesis, in vitro pathway assembly and a scoring system to identify high-performing combinations.