CRISPR/Cas9 screens identify LIG1 as a sensitizer of PARP inhibitors in castration-resistant prostate cancer.

PARP inhibitors (PARPi) have received regulatory approval for the treatment of several tumors, including prostate cancer (PCa), and demonstrate remarkable results in the treatment of castration-resistant prostate cancer (CRPC) patients characterized by defects in homologous recombination repair (HRR) genes. Preclinical studies showed that DNA repair genes (DRG) other than HRR genes may have therapeutic value in the context of PARPi. To this end, we performed multiple CRISPR/Cas9 screens in PCa cell lines using a custom sgRNA library targeting DRG combined with PARPi treatment.

Genetic diversity of dengue virus circulating in the Philippines (2014-2019) and comparison with dengue vaccine strains.

Dengue virus has four distinct serotypes and the genetic diversity within each of the four serotypes contribute to its complexity. An important aspect of dengue molecular evolutionary studies has been the dissection of the extent and structure of genetic variation among major genotypes within each serotype. It is important to understand the role of dengue genetic variability and its potential role and impact in the effectiveness of the dengue vaccine.

Recent and Future Developments in the Use of Poly (ADP-ribose) Polymerase Inhibitors for Prostate Cancer.

Background And Objective: Advanced prostate cancer (PCa) is enriched for alterations in DNA damage repair genes; poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) are a class of drugs that have demonstrated effectiveness in PCa, particularly in tumors with alterations in BRCA1/2 and other homologous recombination repair (HRR) genes, acting through a synthetic lethal mechanism. To prevent or delay drug resistance, and to expand the patient population that can benefit from this class of drug, combination treatment strategies have been developed in preclinical and clinical studies.

Methods: This review examines the latest developments in clinical trials testing PARPi for advanced PCa and their emerging role in earlier disease settings.

Long-Range Proton Channels Constructed via Hierarchical Peptide Self-Assembly.

The quest to understand and mimic proton translocation mechanisms in natural channels has driven the development of peptide-based artificial channels facilitating efficient proton transport across nanometric membranes. It is demonstrated here that hierarchical peptide self-assembly can form micrometers-long proton nanochannels. The fourfold symmetrical peptide design leverages intermolecular aromatic interactions to align self-assembled cyclic peptide nanotubes, creating hydrophilic nanochannels between them.