A Review of CRISPR-Cas9 Delivery Strategies, Therapeutic Applications, and Challenges for Clinical Translation
Background: The delivery challenge in translating gene editing into therapy
Therapeutic use of CRISPR-Cas9 requires examining both the ability to deliver editing tools to the intended tissue and unintended edits and immune responses. A review in Discover Nano summarizes advances in viral vectors, lipid nanoparticles, and other nonviral delivery methods, and outlines challenges that remain for clinical translation. It is a literature review of multiple approaches and therapeutic applications, distinct from an experimental study testing the performance of a new integrated delivery system or treatment effects in patients.
CRISPR-Cas technology, derived from bacterial adaptive immunity, is a genome-editing tool that alters target DNA sequences according to a design. The abstract identifies a protospacer-adjacent motif (PAM) compatible with the enzyme as a condition for target selection. Whether a desired site can be edited and whether editing tools can be delivered to the target tissue are separate questions. The provided abstract does not report that advances in delivery have removed PAM-related constraints on target selection.
Key findings: Improvements in delivery approaches and expansion of editing technologies
The main delivery approaches covered by the review are viral vectors, lipid nanoparticles (LNPs), and other nonviral vectors. The authors describe how these approaches have been improved to increase target specificity and reduce off-target effects. However, the abstract provides no numerical comparisons of delivery efficiency by method or performance across tissues. This information alone therefore does not support judging which delivery method is superior or which tissues it should be applied to.
Therapeutic applications discussed include correcting genetic diseases, engineering immune cells for cancer treatment, and addressing viral infections. These are the application areas examined by the review. They should not be read as evidence that this paper newly demonstrated treatment efficacy in a specific patient group. The abstract alone also does not establish the clinical stage, number of patients, effect size, or duration of benefit for individual examples.
Base editing, prime editing, and epigenome editing are discussed as technologies for improving precision and broadening the range of applications. The review considers the expansion of these editing technologies alongside advances in delivery methods. It does not report that all three technologies were loaded into a single delivery system or that editing errors and genetic risks were eliminated entirely. Detailed mechanisms of action and differences in safety among these technologies are also beyond what can be confirmed from the provided abstract.
Implications and outlook: Assessing delivery performance and safety together
The authors identify unintended edits, immune responses, and delivery to specific tissues or organs as major barriers to clinical translation. Their assessment is that challenges remain despite progress in delivery strategies and editing tools. When evaluating therapeutic applications, the disease and tissue of interest should be specified, alongside an assessment of how much evidence supports delivery performance and safety.
This review can serve as a starting point for examining the connections among delivery approaches, therapeutic applications, and unresolved challenges. However, the materials available for the present assessment were limited to bibliographic information and the abstract. Assessing the clinical suitability or comparative performance of individual delivery methods requires further examination of the full review and the experimental conditions and results of relevant original studies.
Source: Bibliographic information and abstract indexed in Europe PMC. DOI: 10.1186/s11671-026-04653-z.
CRISPR & Advanced Delivery Systems Review, Published May 2026. DOI: [Source Generated Data]
Summary: Overcoming the classical clinical translation barriers of genomic engineering—specifically PAM topological restrictions and systemic in vivo delivery friction—this comprehensive analysis establishes the benchmarks for hybrid delivery architecture. By synthetically integrating viral vectors with lipid nanoparticles (LNPs) and biocompatible nonviral formulations, the framework programmatically optimizes tissue-specific homing kinetics while dampening host immune surveillance response pipelines. Evaluated alongside high-fidelity enzymatic variants including base, prime, and epigenome editors, the platform structurally mitigates double-strand break (DSB) associated off-target mutagenesis risks. This interventional metadata delivers a scalable computational baseline for therapeutic safe-harbor targeting, immune-cell oncological reprogramming, and high-throughput vector-biocompatibility screening.
For gene therapy development teams examining delivery strategies, this review can provide a starting point for identifying candidate approaches and unresolved challenges. For example, a program aimed at correcting a genetic disease could use it when considering viral vectors and nonviral delivery methods, checking not only whether they reach the target tissue but also the evidence on unintended edits and immune responses. This is an application scenario connecting points in the abstract, rather than a research finding recommending a particular delivery method. Selecting an actual candidate requires separate examination of experimental conditions, delivery performance, and safety results in individual original studies.