过去三十年，基因治疗始终被"快递车太小"的魔咒困扰。即便最先进的工程化AAV，也只能运送相当于一本薄册子的基因片段，而治疗遗传性失明、渐冻症等疾病所需的"工具书"常常超重。研究人员尝试过各种"扩容方案"，从压缩基因序列到拆分工具组件，但就像给火箭装自行车轮胎——要么动力不足，要么导航失灵。

然而，AAV载体的包装容量限制了其在递送大基因载荷方面的应用。例如，一些用于基因编辑的工具，如CRISPR–Cas9系统，其基因序列长度超出了AAV载体的包装范围。此外，为了实现细胞类型特异性表达，通常需要在AAV载体中加入增强子等调控元件，这进一步压缩了 ...

CRISPR–Cas12a has a low tolerance for base ... Versatile editors for AAV or RNA delivery To support RNA-based delivery, Ensoma engineered the RNA-processing activity to produce mature messenger ...

They are considered one of the field’s most effective delivery tools ... also now exploring ways to combine AAV vectors with gene-editing tools such as CRISPR/Cas9,” he says.

To assist researchers in the selection of the optimal AAV vector for their application, we have generated a detailed map of viral delivery to tissues in mice, the most commonly used experimental ...

Furthermore, the ABE-based gene editing approach is expected to be less toxic and safer than the conventional CRISPR-Cas9 technology. The AAV genome editing therapy we developed can also be ...