The treatment of patients with advanced-stage solid tumours typically involves a multimodality approach (including surgery, chemotherapy, radiotherapy, targeted therapy and/or immunotherapy), which is often ultimately ineffective. Nucleic acid-based drugs, either as monotherapies or in combination with standard-of-care therapies, are rapidly emerging as novel treatments capable of generating responses in otherwise refractory tumours. These therapies include those using viral vectors (also referred to as gene therapies), several of which have now been approved by regulatory agencies, and nanoparticles containing mRNAs and a range of other nucleotides. In this Review, we describe the development and clinical activity of viral and non-viral nucleic acid-based treatments, including their mechanisms of action, tolerability and available efficacy data from patients with solid tumours. We also describe the effects of the tumour microenvironment on drug delivery for both systemically administered and locally administered agents. Finally, we discuss important trends resulting from ongoing clinical trials and preclinical testing, and manufacturing and/or stability considerations that are expected to underpin the next generation of nucleic acid agents for patients with solid tumours.

晚期实体瘤患者的治疗通常涉及多学科治疗（包括手术、化疗、放疗、靶向治疗和/或免疫治疗），但通常最终无效。基于核酸的药物，无论是作为单一疗法还是与标准护理疗法相结合，都正在迅速成为能够在其他难治性肿瘤中产生反应的新型疗法。这些疗法包括使用病毒载体的疗法（也称为基因疗法），其中一些疗法现已获得监管机构的批准，以及含有 mRNA 和一系列其他核苷酸的纳米颗粒。在这篇综述中，我们描述了基于病毒和非病毒核酸的治疗的开发和临床活性，包括它们的作用机制、耐受性和来自实体瘤患者的可用疗效数据。我们还描述了肿瘤微环境对全身给药和局部给药药物递送的影响。最后，我们讨论了正在进行的临床试验和临床前测试以及制造和/或稳定性考虑所产生的重要趋势，这些趋势预计将支撑用于实体瘤患者的下一代核酸药物。