Jul 2026· International Journal of Drug Delivery Technology· 0 citations· 47 references
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.
This review summarises the current strategies of nanoparticle-mediated CRISPR-Cas9 delivery, including lipid, polymeric, hybrid, inorganic, and biomimetic nanoparticles.
Shouvik Mondal, Kriti Kumari· Advanced International Journ...· 0 citations
A major focus of this review is the inclusion of recent hybrid systems (VLPs, SORT-LNPs) and the recognition that chemical modification of guide RNAs is a critical parameter for therapeutic success and that hybrid systems and stimuli-responsive nanoparticles are poised to dominate the next 5 years of clinical development.
M. Rezaee, F. Izadi, Saeed Nobaharian et al.· Beni-Suef University Journal...· 0 citations
This review focuses on analytical and translational frameworks for CRISPR fidelity assessment, with emphasis on the strengths and limitations of current bioanalytical platforms.
Arpita Mukherjee· Journal of Rare Diseases· 1 citation
The advent of CRISPR/Cas9 genome editing has significantly transformed the landscape of cancer therapeutics by facilitating precise and programmable manipulation of disease-associated genetic modifications. This review comprehensively evaluates the current clinical and translational landscape of CRISPR/Cas9-based cancer therapies through an analysis of published literature and registered clinical trials. The current CRISPR/Cas9 applications in oncology are primarily centred on three mechanistic strategies: immune cell engineering for enhanced tumor recognition, direct targeting of oncogenic mutations, and modulation of tumor-supportive pathways. Analysis of 32 clinical trials indicates that CRISPR-based interventions have demonstrated encouraging safety profiles and early signs of clinical activity, particularly in ex vivo engineered immune-cell therapies. Notable examples include CRISPR-edited CAR-T cell products targeting CD19 and BCMA, which have achieved objective responses in relapsed or refractory hematological malignancies while demonstrating sustained persistence of edited cells in vivo. In contrast, clinical translation into solid tumors remains comparatively limited due to challenges associated with delivery efficiency, tumor heterogeneity, and the immunosuppressive tumor microenvironment. Technological advancements, including multiplex genome editing, base editing, and prime editing have expanded the precision and versatility of CRISPR-based interventions, while integration with immunotherapy and nanotechnology-based delivery systems continues to broaden therapeutic potential. Despite these advances, several significant challenges still need to be addressed, including off-target editing, manufacturing scalability, delivery limitations, and regulatory considerations. Overall, CRISPR/Cas9 represents a promising yet evolving platform in oncology, with its future clinical success dependent on achieving a balance between precision, safety, scalability, and long-term therapeutic durability.
Chu Xin Ng, Sakina Mustafa, X. Y. Yap et al.· Frontiers in Oncology· 0 citations
The continued convergence of nanotechnology and genome engineering may support the development of personalized medicine strategies that adapt genetic engineering tools for patient-specific applications, thereby improving the safety and reliability of gene-editing therapies.
Raheem Mais, Ayush Kumar, Armand Ahmetaj et al.· International Journal of Mol...· 0 citations
CRISPR has progressed from an experimental genome-engineering technology to a clinically relevant therapeutic platform, although its future impact will depend on the ability to combine molecular precision and durable therapeutic benefit with rigorous safety assessment, responsible governance, and equitable access across diverse populations and healthcare systems.
G. Alejandro, Ortega Moreno, G. Amaya et al.· International science journa...· 0 citations