Inlay

Therapeutic strategies against peritoneal metastasis from gastric cancer (GCPM) are limited. Woo and colleagues established a novel syngeneic ACKPY3944-ffluc-GCPM mouse model to test the efficacy of IP CF17 OV treatment. Results showed that CF17 enhanced antitumor activity, immunogenicity, and survival in these mice, supporting its role as a promising immunotherapy for GCPM.

This study evaluates age related effects on CSF delivered lipid-siRNA conjugates, assessing biodistribution, safety, and efficacy. Comparisons between conjugate designs highlights structure dependent performance and provides insight into optimizing siRNA therapeutics for neurodegenerative disease treatment in aged CNS contexts.

Highly-ordered viral proteins like SARS CoV2 RNA-dependent RNA polymerase (RdRp) can evade CD8+ T cell recognition by limiting antigen processing. Increasing protein intrinsic disorder, by dividing RdRp into fragments, boosts immunogenicity and CD8+ T cell responses, offering a simple strategy for vaccines and immunotherapies to overcome viral immune escape responses.

Beckwith-Cohen and colleagues report on successful gene augmentation therapy in a naturally occurring large-animal dog model of cone-rod synaptic disorder due to a mutation in CaBP4. Affected dogs exhibit synaptic immaturity and disorganization, which are rescued even in later stages of the disease supporting significant retinal plasticity.

Glioblastoma (GBM) is among the most formidable of all human cancers. Despite decades of effort, patient outcomes have changed little. The reasons are now all too familiar: extensive genetic heterogeneity, diffuse infiltration into normal brain, profound immune suppression, and the challenge of delivering therapies safely within the central nervous system. Even when targetable mutations are identified, tumors rapidly evolve around them, undermining precision oncology.

In an era defined by the relentless evolution of RNA viruses and the frequent emergence of novel pathogens, the central challenge in infectious disease control lies in matching the pace of pathogen evolution. While nucleic acid-encoded antibodies are not a new concept, with mRNA-encoded monoclonal antibodies (mAbs) having already shown promise in preclinical models of chikungunya, Zika, and HIV, a fundamental disconnect persists. Both mRNA-antibody therapeutics and traditional neutralizing antibody discovery remain heavily reliant on recombinant protein immunogens or convalescent human sera, introducing a “protein bottleneck” that undermines the speed advantage of nucleic acid delivery platforms.

This study uses a new AAV-F capsid to treat a mouse model of pyruvate dehydrogenase complex deficiency, achieving improved survival and disease pathology with a dose ten times lower than the standard AAV9 approach. These findings highlight its strong potential for treating this severe neurodegenerative disorder

RNA-guided endonucleases have rapidly advanced as powerful tools in the field of genome editing, enabling highly precise and targeted genome modifications. The expansion of the genome editing toolbox has been largely driven by CRISPR-Cas systems. However, over the past few years, transposon-derived nucleases from both prokaryotic and eukaryotic systems (identified as evolutionary ancestors of some Cas proteins) have emerged as a new genome editing tool.1,2 TnpB is a family of RNA-guided endonucleases encoded within prokaryotic transposons IS200/605 and IS607 and has evolved into a type-V CRISPR-Cas effector, i.e., Cas12.

QNZ (EVP4593), a selective NF-κB inhibitor, selectively kills myeloma cells while sparing healthy counterparts, suppresses tumor growth in vivo, and synergizes with approved myeloma therapies. These findings establish NF-κB inhibition as a promising and combinable therapeutic strategy in multiple myeloma.