Feng Zhang - Exploration of Biological Diversity to Improve Human Health

Professor Zhang introduced his work on human capsid assembly protein and new RNA editing systems. He described the progress in developing non-viral delivery technologies and shared the discoveries in PNMA2, which was secreted as a non-enveloped capsid and did not selectively package mRNA. After reconstituting PNMA2 capsids in vitro, the group engineered PNMA2 to bind RNA and demonstrated that the engineered PNMA2 could package and deliver mRNA into cells. In the second part, Professor Zhang introduced his work on the IscB protein family. By systematically analyzing the origin and evolutionary relationships of the CRISPR system, they found that the transposon-encoded IscB family proteins were RNA-guided nucleases in the OMEGA (obligate mobile element-guided activity) system, and likely to be the ancestors of the RNA-guided nuclease Cas9 in the type II CRISPR-Cas adaptive immune system. Using evolutionary analysis, RNA sequencing, and biochemical experiments, Zhang’s lab demonstrated that IscB used a single ncRNA for RNA-guided cleavage of dsDNA, and it could be harnessed for genome editing in human cells. This work revealed a widespread class of transposon-encoded RNA-guided nucleases, with strong developability as biotechnologies for gene editing and gene delivery.