Plant-based siRNA could bring a "green revolution" to RNAi tools and therapies

"Green Revolution" in the early 1950s, the extensive cultivation of dwarf rice solves the food problem in developing countries. At present, chronic infection with the hepatitis B virus (HBV) is a major public health problem. According to the World Health Organization (WHO) announcement, approximately 257 million people are chronically infected with hepatitis B. Recent studies have shown that the level of expression of the antigen gene Hepatitis B virus (HBsAg) surface area is correlated with the presence of HCC or fibrosis severity in transgenic mice and patients infected with HBV, therefore, HBsAg becomes an increasingly important target for the design of drugs for the treatment of hepatitis B.

In a study recently published in biomaterialsDr. Zhi Hong and Dr. Chen-Yu Zhang of Nanjing University and their collaborators report that small silent RNA sequences directed against HBsAg generated in edible lettuce (Lactuca sativa L.) can specifically bind and inhibit gene expression in inactivated p21-HBsAg transgenic mice at a relatively small amount compared to synthetic siRNAs. Most importantly, continued administration of a decoction containing a amiRNA relieves liver damage in transgenic mice without additional negative effects even after a 15-month treatment.

This work uses the plant's endogenous microRNA biogenesis machinery to produce short methylated interfering sequences to increase the stability of target siRNAs while reducing production costs. Therefore, these works not only provide an affordable treatment strategy for patients with chronic hepatitis B in developing countries, but also reduce the required dose of RNAi-based drugs to minimize the effects Potential side effects of RNAi treatment and allow administration for a relatively long period or together. with other antiviral drugs.

For patients who are in the immune tolerance phase or who are resistant to conventional antiviral treatment, this RNAi-based treatment can effectively reduce their risk of liver injury through the daily consumption of a decoction of HBsAg-inhibiting RNA-containing vegetables.

In the long term, this method could also be applied to the treatment of hepatitis C or other infectious diseases because of the effective, less toxic and financially viable strategy for producing short interfering sequences using modified plants. It can be predicted that plant-derived siRNAs will bring a "green revolution" in RNAi-based tools and treatments.

When we look back, the green revolution brought us a richer food supply. At the same time, we should also know that daily food changes too, in which the small RNAs we take can play an important role.

Source:

School of Life Sciences of Nanjing University

Journal reference:

Zhang, S. et al. (2019) RNAi Therapeutic Products of Plant Origin: A Strategic Inhibitor of HBsAg. biomaterials. doi.org/10.1016/j.biomaterials.2019.04.033.