Search

Despite the exciting promise of cancer immunotherapy in the clinic, immune checkpoint blockade therapy and T cell-based therapies are often associated with low response rates, intrinsic and adaptive immune resistance, and systemic side effects. CRISPR-Cas-based genome editing appears to be an effective strategy to overcome these unmet clinical needs. As a safer delivery platform for the CRISPR-Cas system, non-viral nanoformulations have been recently explored to target tumor cells and immune cells, aiming to improve cancer immunotherapy on a gene level. In this review, we summarized the efforts of non-viral vector-based CRISPR-Cas-mediated genome editing in tumor cells and immune cells for cancer immunotherapy. Their design rationale and specific applications were highlighted.

Clustered regularly interspaced short palindromic repeats/associated protein 9 (CRISPR/Cas9) gene-editing technology shows promise for manipulating single or multiple tumor-associated genes and engineering immune cells to treat cancers. Currently, most gene-editing strategies rely on viral delivery; yet, while being efficient, many limitations, mainly from safety and packaging capacity considerations, hinder the use of viral CRISPR vectors in cancer therapy. In contrast, recent advances in non-viral CRISPR/Cas9 nanoformulations have paved the way for better cancer gene editing, as these nanoformulations can be engineered to improve safety, efficiency, and specificity through optimizing the packaging capacity, pharmacokinetics, and targetability. In this review, the advance in non-viral CRISPR delivery is highlighted, and there is a discussion on how these approaches can be potentially used to treat cancers in addressing the aforementioned limitations, followed by the perspectives in designing a proper CRISPR/Cas9-based cancer nanomedicine system with translational potential., (© 2023 Wiley‐VCH GmbH.)

The CRISPR-Cas9 technology has changed the landscape of genome editing and has demonstrated extraordinary potential for treating otherwise incurable diseases. Engineering strategies to enable efficient intracellular delivery of CRISPR-Cas9 components has been a central theme for broadening the impact of the CRISPR-Cas9 technology. Various non-viral delivery systems for CRISPR-Cas9 have been investigated given their favorable safety profiles over viral systems. Many recent efforts have been focused on the development of stimuli-responsive non-viral CRISPR-Cas9 delivery systems, with the goal of achieving efficient and precise genome editing. Stimuli-responsive nanoplatforms are capable of sensing and responding to particular triggers, such as innate biological cues and external stimuli, for controlled CRISPR-Cas9 genome editing. In this Review, we overview the recent advances in stimuli-responsive nanoformulations for CRISPR-Cas9 delivery, highlight the rationale of stimuli and formulation designs, and summarize their biomedical applications., (© 2022. The Author(s).)