Precise RNA targeting with CRISPR-Cas13d.

The possibility of collateral RNA degradation poses a concern for transcriptome perturbations and therapeutic applications using CRISPR-Cas13. We show that collateral activity only occurs with high RfxCas13d expression. Using low-copy RfxCas13d in transcriptome-scale and combinatorial pooled screens, we achieve high on-target knockdown without extensive collateral activity.

Guselkumab Efficacy by Psoriasis Disease Severity and Treatment History: VOYAGE 1 and 2 Post Hoc Analyses.

Background: The pivotal Phase 3 VOYAGE 1 and VOYAGE 2 studies established the robust efficacy and safety of guselkumab for up to 5 years in patients with moderate-to-severe psoriasis. Here, the long-term efficacy of guselkumab by baseline disease severity and treatment history was analyzed using pooled data from the VOYAGE studies.

Methods: Patients were randomized to guselkumab 100 mg every 8 weeks, placebo with week 16 crossover to guselkumab, or adalimumab with week 52 crossover to guselkumab (VOYAGE 1) or week 28-76 randomized withdrawal/re-treatment (VOYAGE 2); all patients then received open-label guselkumab through week 252.

High-dose ascorbic acid synergizes with anti-PD1 therapy in non-small cell lung cancer and models.

Introduction: Immune checkpoint inhibitors(ICIs) targeting programmed cell death protein 1 (PD1) confer significant survival benefits to patients with non-small cell lung cancer (NSCLC). However, there remains a substantial unmet need to identify therapeutic approaches to overcome resistance and provide benefits to these patients. High-dose ascorbic acid (AA) acts synergistically with many standard anticancer treatments.

Improving Diversity in a Novel Psoriasis Study: VISIBLE as a Framework for Clinical Trial Quality Improvement.

Importance: Diverse racial and ethnic representation in clinical trials has been limited, not representative of the US population, and the subject of pending US Food and Drug Administration guidance. Psoriasis presentation and disease burden can vary by skin pigmentation, race and ethnicity, and socioeconomic differences. Overall, there are limited primary data on clinical response, genetics, and quality of life in populations with psoriasis and skin of color (SoC).

Transcriptome-scale RNA-targeting CRISPR screens reveal essential lncRNAs in human cells.

Mammalian genomes host a diverse array of RNA that includes protein-coding and noncoding transcripts. However, the functional roles of most long noncoding RNAs (lncRNAs) remain elusive. Using RNA-targeting CRISPR-Cas13 screens, we probed how the loss of ∼6,200 lncRNAs impacts cell fitness across five human cell lines and identified 778 lncRNAs with context-specific or broad essentiality.