Delivery of genetic material to tissues in vivo is an important technique used in research settings and is the foundation upon which clinical gene therapy is built. The lung is a prime target for gene delivery due to a host of genetic, acquired, and infectious diseases that manifest themselves there, resulting in many pathologies. However, the in vivo delivery of genetic material to the lung remains a practical problem clinically and is considered the major obstacle needed to be overcome for gene therapy. Currently there are four main strategies for in vivo gene delivery to the lung: viral vectors, liposomes, nanoparticles, and electroporation. Viral delivery uses several different genetically modified viruses that enter the cell and express desired genes that have been inserted to the viral genome. Liposomes use combinations of charged and neutral lipids that can encapsulate genetic cargo and enter cells through endogenous mechanisms, thereby delivering their cargoes. Nanoparticles are defined by their size (typically less than 100 nm) and are made up of many different classes of building blocks, including biological and synthetic polymers, cell penetrant and other peptides, and dendrimers, that also enter cells through endogenous mechanisms. Electroporation uses mild to moderate electrical pulses to create pores in the cell membrane through which delivered genetic material can enter a cell. An emerging fifth category, exosomes and extracellular vesicles, may have advantages of both viral and non-viral approaches. These extracellular vesicles bud from cellular membranes containing receptors and ligands that may aid cell targeting and which can be loaded with genetic material for efficient transfer. Each of these vectors can be used for different gene delivery applications based on mechanisms of action, side-effects, and other factors, and their use in the lung and possible clinical considerations is the primary focus of this review.

将遗传物质递送至体内组织是研究环境中使用的一项重要技术，也是临床基因治疗的基础。肺部是基因传递的主要目标，因为许多遗传性疾病、获得性疾病和传染病都在肺部表现出来，从而导致许多病症。然而，将遗传物质体内递送至肺部仍然是临床上的实际问题，并被认为是基因治疗需要克服的主要障碍。目前，体内基因递送至肺部有四种主要策略：病毒载体、脂质体、纳米颗粒和电穿孔。病毒递送使用几种不同的转基因病毒，这些病毒进入细胞并表达已插入病毒基因组的所需基因。脂质体使用带电和中性脂质的组合，可以封装遗传货物并通过内源机制进入细胞，从而递送其货物。纳米颗粒由其尺寸（通常小于 100 nm）定义，由许多不同类别的构建块组成，包括生物和合成聚合物、细胞渗透剂和其他肽以及树枝状聚合物，它们也通过内源机制进入细胞。电穿孔使用轻度至中度的电脉冲在细胞膜上形成孔，传递的遗传物质可以通过这些孔进入细胞。新兴的第五类，外泌体和细胞外囊泡，可能具有病毒和非病毒方法的优点。这些细胞外囊泡从含有受体和配体的细胞膜上萌芽，这些受体和配体可以帮助细胞靶向，并且可以装载遗传物质以进行有效转移。 根据作用机制、副作用和其他因素，这些载体中的每一种都可用于不同的基因递送应用，它们在肺部的使用和可能的临床考虑是本次综述的主要焦点。