🧬 PubMed RNA Editing Daily Digest

Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) form RNA-guided adaptive immune systems in bacteria and archaea that mediate sequence-specific defense against invading genetic elements. Beyond their ecological role in restricting bacteriophage infection and horizontal gene transfer (HGT), CRISPR-Cas systems have been repurposed as programmable nucleases, enabling rapid, scalable, and precise genome engineering. Over the past decade, CRISPR platforms, most prominently Cas9, have transformed functional genomics, accelerated target discovery and drug development, and progressed from experimental tools to clinically evaluated gene and cell therapies. In parallel, growing attention has focused on both native and engineered roles of CRISPR-Cas in shaping HGT, plasmid ecology, and antimicrobial resistance (AMR), as AMR continues to expand globally. In this Review, we integrate advances spanning eukaryotic genome editing and prokaryotic antimicrobial applications. We summarize CRISPR-Cas classification and molecular mechanisms, highlighting spacer acquisition, guide RNA biogenesis, target recognition, and nucleic acid cleavage. We then examine how cellular DNA repair pathways influence editing outcomes and discuss strategies to enhance precision. We further review delivery strategies, such as conjugative plasmids, bacteriophages and phagemids, extracellular vesicles, and nanoparticles, together with evolutionary countermeasures encoded by mobile genetic elements, including anti-CRISPR proteins. Finally, we outline current limitations.

CRISPR/Cas systems, initially characterized as bacterial adaptive immune mechanisms, have rapidly emerged as precise and versatile genome-editing tools with significant potential for antiviral research and therapeutic development. This review highlights the role of CRISPR/Cas systems in targeting persistent and human oncogenic viruses, including HPV, HBV, HCV, EBV, KSHV, HTLV-1, and MCPyV, as well as HIV, which may indirectly contribute to cancer through immune dysregulation. Many of these viruses can integrate into the host genome or persist as chronic or latent infections, contributing to cancers for which curative options are limited. CRISPR-based strategies enable the excision of integrated proviral DNA, disruption of viral replication, targeted silencing of viral transcripts, and modulation of host tumor-suppressor pathways. Cas9 efficiently targets DNA viruses, such as HBV and HPV, whereas RNA-targeting Cas13 allows precise silencing of RNA viruses, like HCV. Editing T-cell receptors, including CCR5 and CXCR4, offers the potential for long-term resistance to HIV. CRISPR-based preclinical studies indicate the potential to disrupt HBV cccDNA, suppress EBV and KSHV latency gene expression, and inactivate HTLV-1 oncogenes, thereby potentially reducing viral persistence and oncogenic progression. Despite these advances, challenges remain regarding off-target effects, delivery efficiency, immune responses, and ethical considerations. Innovations such as high-fidelity Cas variants, base and prime editing, and non-viral delivery systems are expected to enhance both safety and therapeutic precision. This review provides an overview of viral life cycles, oncogenic pathways, and therapeutic vulnerabilities of human oncogenic viruses and CRISPR-based genome-editing approaches under investigation for viral elimination and cancer therapy.