Song Zhidu, Tao Ying, Liu Yue, Li Jian
Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, China.
Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, China.
Front Immunol. 2024 Aug 30;15:1444437. doi: 10.3389/fimmu.2024.1444437. eCollection 2024.
The delivery of CRISPR/Cas systems holds immense potential for revolutionizing cancer treatment, with recent advancements focusing on extracellular vesicles (EVs) and viral vectors. EVs, particularly exosomes, offer promising opportunities for targeted therapy due to their natural cargo transport capabilities. Engineered EVs have shown efficacy in delivering CRISPR/Cas components to tumor cells, resulting in inhibited cancer cell proliferation and enhanced chemotherapy sensitivity. However, challenges such as off-target effects and immune responses remain significant hurdles. Viral vectors, including adeno-associated viruses (AAVs) and adenoviral vectors (AdVs), represent robust delivery platforms for CRISPR/Cas systems. AAVs, known for their safety profile, have already been employed in clinical trials for gene therapy, demonstrating their potential in cancer treatment. AdVs, capable of infecting both dividing and non-dividing cells, offer versatility in CRISPR/Cas delivery for disease modeling and drug discovery. Despite their efficacy, viral vectors present several challenges, including immune responses and off-target effects. Future directions entail refining delivery systems to enhance specificity and minimize adverse effects, heralding personalized and effective CRISPR/Cas-mediated cancer therapies. This article underscores the importance of optimized delivery mechanisms in realizing the full therapeutic potential of CRISPR/Cas technology in oncology. As the field progresses, addressing these challenges will be pivotal for translating CRISPR/Cas-mediated cancer treatments from bench to bedside.
CRISPR/Cas系统的递送在彻底改变癌症治疗方面具有巨大潜力，近期的进展集中在细胞外囊泡（EVs）和病毒载体上。EVs，特别是外泌体，由于其天然的货物运输能力，为靶向治疗提供了有前景的机会。工程化的EVs已显示出将CRISPR/Cas组件递送至肿瘤细胞的功效，从而抑制癌细胞增殖并增强化疗敏感性。然而，脱靶效应和免疫反应等挑战仍然是重大障碍。病毒载体，包括腺相关病毒（AAVs）和腺病毒载体（AdVs），是CRISPR/Cas系统强大的递送平台。以其安全性著称的AAVs已被用于基因治疗的临床试验，证明了它们在癌症治疗中的潜力。AdVs能够感染分裂和非分裂细胞，在用于疾病建模和药物发现的CRISPR/Cas递送中具有多功能性。尽管它们有效，但病毒载体也存在一些挑战，包括免疫反应和脱靶效应。未来的方向需要改进递送系统以提高特异性并将不良反应降至最低，从而带来个性化且有效的CRISPR/Cas介导的癌症治疗。本文强调了优化递送机制在实现CRISPR/Cas技术在肿瘤学中的全部治疗潜力方面的重要性。随着该领域的发展，应对这些挑战对于将CRISPR/Cas介导的癌症治疗从实验室转化到临床至关重要。
