Green Tea and Probiotics Used to Encapsulate RNA in ‘Nanomissile’ for Inflammatory Bowel Disease

Chinese researchers have developed a “nanomissile” technology that uses green tea compounds and probiotic-derived materials to precisely deliver an oral RNA therapeutic to sites of intestinal inflammation.

According to Chinese biotech media outlet BioOn on the 6th, a research team led by Professor Ryu Song-bae of Zhejiang University published the findings in the international journal Science Advances on March 27 (local time). Oral RNA drugs have limited stability and are difficult to deliver to target sites because of the complex gastrointestinal environment and various degradative enzymes.

To address this problem, the researchers designed a drug delivery vehicle using polyphenols, the major bioactive compounds in tea, and probiotic-derived “outer membrane vesicles (OMVs).” First, they modified the food-grade green tea polyphenol “epigallocatechin (EGC)” to create nanovesicles that encapsulate therapeutic RNA.

They then fused the nanovesicles with outer membrane vesicles derived from the probiotic “Escherichia coli Nissle 1917 (E. coli Nissle 1917)” to create stable hybrid vesicles. The outer membrane vesicles serve as “armor,” stably protecting their contents even in the gastrointestinal environment.

The researchers further increased targeting precision by attaching the ligand HA-BR-KDEL, which sequentially targets specific cells and intracellular organelles. Hyaluronic acid (HA) identifies inflammatory cells, while the KDEL peptide targets the endoplasmic reticulum, an intracellular organelle.

In this study, the researchers loaded the system with siRNA that inhibits the pro-inflammatory cytokine “tumor necrosis factor-alpha (TNF-α).” When the oral therapeutic was administered to a mouse model of induced colitis, the researchers observed significant alleviation of colitis symptoms and restoration of intestinal homeostasis.

The researchers said their “tea polyphenol hybrid outer membrane vesicle” strategy offers a new possibility for developing oral gene therapies for chronic diseases such as inflammatory bowel disease.