最近有文章报道一则关于一位基因治疗的病人治疗失败去世的消息。去年10月，Terry,一位27岁的杜氏肌营养不良症（DMD）患者，在接受一种为其量身定制的基因治疗的8天后，离开了人世。Terry是那次临床试验的唯一一个入组患者。这项临床试验由一家名为Cure Rare Disease的非营利性机构发起，而它的创始人正是Terry的哥哥Rich Horgan。
在文章中提到未来会测试和开发新的AAV突变体AAVMYO。AAVMYO是海德堡大学研究员Dirk Grimm设计的新版本AAV。下面我们来看看他们是如何发现这个有效的突变体的。
A robust workflow for massively parallel in vivo AAV capsid stratification.
a Experimental setup. Shown are the essential experimental and bioinformatic steps, from the (i) cloning of barcoded YFP reporter vectors, (ii) library production, and (iii) animal (mouse here) injection, to (iv) tissue harvest and NGS, followed by (v) data analysis. Also shown is a timeline for the entire workflow or the individual steps. Note that the exact time required in step (ii) depends on the size of the library. Likewise, the time to perform the final bioinformatic analysis in step (v) is determined by available computing (IT) power. The first step (orange arrow) can be skipped if users start with our pre-existing collection of barcoded vector genomes, which will cut down the required overall time to <6 months. Please see the main text for further details. b Ranking of capsids in all three libraries by transcriptional efficiency (Vαβ) in the pancreas. Shown are the top ten AAV variants and the proportion of their transcriptional efficiency after normalization to all capsids or barcodes, respectively, in each library. Depicted values are the average from six C57BL/6 J mice with SD. BC, barcode; i.v., intravenous. This figure contains clipart from Servier Medical Art. Source data are available in the Source data file.
ref: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7595228/
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