A conserved pilin from uncultured gut bacterial clade TANB77 enhances cancer immunotherapy.

Immune checkpoint blockade (ICB) has become a standard anti-cancer treatment, offering durable clinical benefits. However, the limited response rate of ICB necessitates biomarkers to predict and modulate the efficacy of the therapy. The gut microbiome's influence on ICB efficacy is of particular interest due to its modifiability through various interventions.

Molecular characterization of the archaic HLA-B*73:01 allele reveals presentation of a unique peptidome and skewed engagement by KIR2DL2.

HLA class I alleles of archaic origin may have been retained in modern humans because they provide immunity against diseases to which archaic humans had evolved resistance. According to this model, archaic introgressed alleles were somehow distinct from those that evolved in African populations. Here we show that HLA-B*73:01, a rare allotype with putative archaic origins, has a relatively rare peptide binding motif with an unusually long-tailed peptide length distribution.

Lipid Nanoparticle-Mediated CRISPR-Cas13a Delivery for the Control of Bacterial Infection.

Lipid nanoparticles (LNPs) can assist in the delivery of nucleic acid inside animal cells, as demonstrated by their use in COVID-19 vaccine development. However, LNPs applicable to bacteria have not been reported. Here, the screening of 511 LNPs containing random combinations of different lipid components identified two LNPs, LNP 496 and LNP 470, that efficiently delivered plasmids into Escherichia coli BW25113.

A Novel Self-Amplifying mRNA with Decreased Cytotoxicity and Enhanced Protein Expression by Macrodomain Mutations.

The efficacy and safety of self-amplifying mRNA (saRNA) have been demonstrated in COVID-19 vaccine applications. Unlike conventional non-replicating mRNA (nrmRNA), saRNA offers a key advantage: its self-replication mechanism fosters efficient expression of the encoded protein, leading to substantial dose savings during administration. Consequently, there is a growing interest in further optimizing the expression efficiency of saRNA.