: Viruses have been repurposed into tools for gene delivery by transforming them into viral vectors. The most frequently used vectors are lentiviral vectors (LVs), derived from the human immune deficiency virus allowing efficient gene transfer in mammalian cells. They represent one of the safest and most efficient treatments for monogenic diseases affecting the hematopoietic system. LVs are modified with different viral envelopes (pseudotyping) to alter and improve their tropism for different primary cell types. The vesicular stomatitis virus glycoprotein (VSV-G) is commonly used for pseudotyping as it enhances gene transfer into multiple hematopoietic cell types. However, VSV-G pseudotyped LVs are not able to confer efficient transduction in quiescent blood cells, such as hematopoietic stem cells (HSC), B and T cells. To solve this problem, VSV-G can be exchanged for other heterologous viral envelopes glycoproteins, such as those from the Measles virus, Baboon endogenous retrovirus, Cocal virus, Nipah virus or Sendai virus. Here, we provide an overview of how these LV pseudotypes improved transduction efficiency of HSC, B, T and natural killer (NK) cells, underlined by multiple in vitro and in vivo studies demonstrating how pseudotyped LVs deliver therapeutic genes or gene editing tools to treat different genetic diseases and efficiently generate CAR T cells for cancer treatment.

中文翻译：

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慢病毒载体假型：为研究和基因治疗改善造血细胞基因修饰的宝贵工具。

： 通过将病毒转化为病毒载体，它们已被重新用于基因传递工具。最常用的载体是慢病毒载体（LVs），其衍生自人类免疫缺陷病毒，可在哺乳动物细胞中进行有效的基因转移。它们代表了影响造血系统的单基因疾病的最安全，最有效的治疗方法之一。用不同的病毒包膜（假型）修饰LV，以改变和改善其对不同原代细胞类型的向性。水泡性口炎病毒糖蛋白（VSV-G）通常用于假型化，因为它可以增强基因向多种造血细胞类型的转移。但是，VSV-G假型LV不能在静态血细胞（如造血干细胞（HSC），B和T细胞）中提供有效的转导。为了解决这个问题，VSV-G可以交换其他异源病毒包膜糖蛋白，例如来自麻疹病毒，狒狒内源性逆转录病毒，Cocal病毒，Nipah病毒或仙台病毒的糖蛋白。在这里，我们提供了这些LV假型如何改善HSC，B，T和自然杀伤（NK）细胞转导效率的概述，并通过多项体外和体内研究强调了这一点，这些研究表明假型LV可以如何递送治疗性基因或基因编辑工具来治疗不同的遗传疾病，并有效产生可治疗癌症的CAR T细胞。