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An important consideration is the balance between the extracellular stability and
intracellular disassembly to allow RNAi trigger release and subsequent interaction
with the RNAi machinery.
Tremendous progress has been made in our understanding of intracellular
trafficking of RNAi vectors over the past several years. As increasing numbers of
researchers join the field of RNAi delivery, we will undoubtedly see further prog-
ress, which will translate better understanding of the underlying processes to design-
ing more efficacious delivery vectors. The improvements in delivery vectors will be
closely tied with the rapidly developing field of nanotechnology, especially in areas
of multifunctional delivery systems that will permit improved integration of multi-
ple functionalities into RNAi delivery vectors. Major shortcoming of the current
research on intracellular trafficking of RNAi delivery vectors has been its almost
exclusive focus on in vitro experiments. Considering how poorly translatable and
predictive these findings have so far been to in vivo conditions, it is important that
future research focuses on enhancing our understanding of intracellular trafficking
of RNAi vectors in vivo.
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