Target validation through protein- domain knockout - applications of intracellularly stable single-chain antibodies
2002
The human genome project has delivered a large number of genes and respective proteins that await to be validated as potential drug targets.Such a complexity has made target validation the main bottleneck in today’s drug development process. In addition, the majority of these new potential targets are proteins that function intracellularly.Approaches such as gene knockout, antisense RNA or RNA interference (RNAi) are currently used to validate candidate drug targets by analysing the effects of their deletion. Intrabodies (single-chain antibodies expressed within the cell) present an attractive alternative for directly modulating protein function in vivo. In particular, intrabodies can be used to target specific domains of a protein and perform so-called ‘protein-domain knockouts’, thus allowing the dissection of the varied functions of multi-domain proteins.
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