Advanced CRISPR-Cas Genome Engineering Coupled with Nanotechnology-Based Drug Delivery for Treating Genetic and Infectious Diseases
Abstract
Background CRISPR-Cas genome editing offers curative potential for monogenic disorders and persistent infections, but its clinical translation is hindered by delivery inefficiency, off-target effects, and immunogenicity. Nanocarrier platforms address these barriers by enabling targeted, transient intracellular delivery of CRISPR components. Methods This PRISMA 2020–guided systematic review and meta-analysis synthesized data from 127 preclinical studies and 14 Phase I/II clinical trials (2018–2025) evaluating CRISPR-nanocarrier systems. Results Pooled analysis revealed a median on-target editing efficiency of 52.4% (95% CI: 48.1–56.7). Ionizable lipid nanoparticles (LNPs) demonstrated superior hepatic delivery, while engineered extracellular vesicles (EVs) enabled extrahepatic tropism. Safety profiles were highly favorable: off-target edits remained consistently <0.1%, chromosomal aberrations were negligible (98.4% compliance), and pathogen loads decreased by 3.12 log₁₀. Functional protein restoration yielded a large pooled effect size (SMD: 2.84). Adverse events were primarily limited to transient cytokine elevation and mild, manageable hepatotoxicity. Carrier architecture and ribonucleoprotein (RNP) cargo format emerged as significant predictors of editing success. Conclusion CRISPR-nanocarrier systems represent a highly viable precision medicine platform for achieving durable, potentially curative outcomes. Accelerating clinical deployment requires prioritizing standardized GMP manufacturing, longterm genomic surveillance, scalable access frameworks, and the continued optimization of stimuli-responsive carriers and high-fidelity editors.