Gene Inhibition Therapy

shRNA Versus Artificial miRNA

A summary of the key differences between shRNA and artificial microRNA.

Let’s now summarize the key differences between shRNA and artificial microRNA.

The use of shRNA results in specific gene knockdown and high levels of shRNA expression. This strategy has been used widely because of the simple design, long-term expression, and stability of shRNA. The high levels of shRNAs can potentially oversaturate the endogenous RNAi pathway and result in possible non-specific toxicity. However, structural modifications have been made to address these issues18,47-50.

In contrast, artificial microRNAs result in less specific gene knockdown and typically lower level of expression. These properties make artificial microRNAs less likely to disrupt endogenous RNAi pathways than shRNAs, which lowers the risk of non-specific toxicity18,47,51.

Because of their simple design and long-term expression and stability, shRNAs have been investigated in a wide variety of applications, including myocardial ischemia, HIV, and tumor growth18,52,53.

Artificial microRNAs have also been investigated in a variety of diseases such as hepatitis B54,55, amyotrophic lateral sclerosis56, facioscapulohumeral muscular dystrophy57, and Huntington’s disease58.

Because all cases of Huntington’s disease are caused by the same basic mutation that results in the accumulation of a mutant protein, it is an ideal target for gene inhibition therapies59. In Huntington’s disease, mutations in the huntingtin or HTT gene lead to a toxic accumulation of the mutant HTT protein in the brain, which causes massive neurodegeneration and clinical symptoms associated with the disease60. By selectively reducing mutant HTT expression, gene inhibition strategies could reverse the pathological features of Huntington’s disease associated with aberrant accumulation of HTT protein60.

This concludes the module on how gene inhibition therapy works. Please return to the Education Center to learn more about gene inhibition and other gene therapy mechanisms.

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