Silencing genes in the kidney: antisense or RNA interference?

Targeting genes in disease has long been a sought-after holy grail, with the concept of gene therapy promising a magic bullet for single gene mutation or deletion disorders. Replacing deficient or non-functional genes with the active form has proven more difficult to achieve than originally hoped. However, a subset of gene therapy termed ‘gene silencing’ is being developed, which is altogether more promising. By utilizing the unique nature of gene-sequence specificity, complementary or antisense molecules can be designed to ‘seek and destroy’ target mRNAs for specific proteins known to be pivotal in the pathogenesis of various disease processes. Two strategies have been employed to silence genes; the first involves the use of single-stranded antisense oligodeoxynucleotides (ASO) and the second uses double-stranded short-interfering RNA molecules (siRNA) otherwise known as RNA interference (RNAi).