常用的定向进化开发策略总结如下: 1.通过Capsid shuffling(衣壳重组)或Error-prone(易错)PCR等方法进行定向进化可以创建许多独特的衣壳组合,这些衣壳组合可能具有独特和有利的载体特性。 2.开发非人类来源的衣壳序列,可能避免人类体内已经存在的多种血清型抗体的免疫封锁。 3.利用现有的衣壳生物学知识和宿主细胞靶点来合理...
它可以在灵长类动物的肝脏等组织中非常有效地进行基因递送;③嵌合型的AV-DJ,它由8个不同的野生型AAV进行DNA shuffling后得到,它不单在多种类型的细胞中都有效,并且还比母本之一的AAV2更具有免疫逃避性。
The AAV-DJ system provides a hybrid capsid created by DNA shuffling technology combining 8 different native serotypes: AAV-2, AAV-4, AAV-5, AAV-8, AAV-9, avian AAV, bovine AAV, and caprine AAV. The result is a highly infectious vector that can transduce a wide variety of cells and ...
[48]. In addition, recombinant techniques involving capsid shuffling, directed evolution, and random peptide library insertions are being utilized to derive variants of known AAVs with unique attributes [49,50,51]. In vivo-directed evolution has been successfully used to identify novel AAV variants...
We hypothesized that capsid library screens in human skeletal muscle cells both in vitro and in vivo would be an ideal route to accomplish these goals. We utilized wild-type replicating AAV libraries of 10e5 variants via DNA shuffling of eleven different parental AAV capsids. Our libraries ...
We thus compared the AAV9 capsid currently used in the FDA approved gene therapy for spinal muscular atrophy (SMA) (onasemnogene abeparvovec-xioi) to the AAV-DJ synthetic capsid that was developed by shuffling naturally occurring serotypes [20]. AAV-DJ was recently demonstrated to be ...
Generation of AAV-DJ through Capsid DNA Family Shuffling. Recent Product Citations Alsalloum, M. et al. (2023). A truncated receptor TRKB isoform (TRKB.T1) in mechanisms of genetically determined depressive-like behavior of mice.Biomedicines.11(9):2573. doi: 10.3390/biomedicines11092573. ...
Adeno-associated Viral VectorsAAV Gene TherapyDNA Family ShufflingSynthetic VectorsTherapeutic Human Gene TransferRecombinant VectorsAAV SerotypesNatural VirusesSynthetic AAV VectorsDNA FragmentationAAV Capsid GenesPeptide DisplayHigh-throughput Method Play
capsid DNA shuffling, manipulating AAV capsid DNA by DNA shuffling or error prone PCR creates an AAV capsid library which contains substantial diversity (Asokan et al.,Mol. Ther.20:699 (2012)). Subsequent administration of this library either in vitro or in vivo provides the means to rescue n...
The disclosure relates to compositions, methods, and processes for the preparation, use, and/or formulation of adeno-associated virus capsid proteins, wherein the capsid proteins co