‘Green Revolution’ in RNAi Tools and Therapeutics

In the early 1950s, 'green revolution' is the extensive cultivation of Dwarf Rice to solve the food problem in developing countries. Recently, chronic infection with hepatitis B virus (HBV) has been a significant public health problem. The World Health Organization announced recently that an estimated 257 million people are chronically infected with hepatitis B. In the current research, it was revealed that the expression level of hepatitis B virus surface antigen gene (HBsAg) is connected with the occurrence of HCC or fibrosis severity in transgenic mice and HBV infection patients; therefore, HBsAg becomes a rising target for drug design for the treatment of hepatitis B.

Dr. Zhi Hong and Dr. Chen-Yu Zhang from Nanjing University have collaborated reported in a study published in Biomaterials that the small silencing RNA sequences against HBsAg generated in edible lettuce (Lactuca sativa L.) can specifically bind and inhibit gene expression in p21-HBsAg knock-in transgenic mice at a relatively low amount when compared to synthetic siRNAs. More importantly, continuous administration of amiRNA-containing decoction relieves the liver injury in transgenic mice without other adverse effects even after 15-month treatment.

The researchers utilized the plant-endogenous microRNA biogenesis machinery for this work to produce methylated short interfering sequences for increasing the stability of target siRNAs while reducing the cost of production.

As a result, this work does not only offer an affordable treatment strategy for chronic hepatitis B patients in developing countries but also reduces the required dose of RNAi drugs to minimize the potential side effects of RNAi therapy and allow the administration for a relatively long period or in conjunction with other antiviral drugs.

For all patients in the immune-tolerant phase or resistant to conventional antivirus treatment, this RNAi-based therapy may effectively reduce their risk of liver injury by daily consumption of vegetable decoction containing HBsAg silencing RNAs.

Also, taking a long perception, this technique may apply to the treatment of hepatitis C other infectious diseases due to the practical, less toxic and financially viable strategy to produce short interfering sequences using engineered plants. It can be predicted that plant-derived siRNAs will bring a "green revolution" in RNAi tools and therapeutics.

Also, looking back, according to the researchers, the Green Revolution has brought humans more abundant food supply. At the same time, we should also know that the daily food is also changing ourselves, in which the small RNAs we take from food may play an important role.

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