RNAi Therapy: Antibodies guide the way
A weakness of the fusion proteins used by the authors is that purification and refolding steps are needed for each recombinant fusion protein. This might be addressed by the production of soluble antibodies with phage display technology.16 Despite the limitations mentioned above, there is no doubt that antibody targeting is an attractive strategy for the selective delivery of siRNAs. The potential of the method is by no means limited to synthetic siRNAs and may be extended to gene-encoding hairpin siRNAs, which are potentially useful for maintaining sustained expression of siRNAs.
Transcriptional targeting, whereby regulatory sequences from tissue-specific genes are used to control the expression of siRNAs, should represent an additional viable strategy. For example, it may be possible to restrict siRNA expression to cancer cells by placing the siRNA under the control of a promoter taken from a gene selectively expressed in cancer cells. The successful delivery or expression of siRNAs in a desired cell population will undoubtedly have great therapeutic applications in treating various human diseases.
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