Critique of a rat liver experiment: different delivery schemes for genetic instructions encoding two sets of proteins

Critique of a rat liver experiment: different delivery schemes for genetic instructions encoding two sets of proteins

On October 18, Yuri Deigin examined the design of an experiment comparing OSK and OSKM in male rats in a thread. In models of chronic liver disease, OSK reduced injury and fibrosis; in one model, OSKM was associated with tumors and lower survival.

OSK and OSKM are sets of Yamanaka factors, proteins that can temporarily change how cells function. OSK comprises Oct4, Sox2 and Klf4; OSKM contains the same proteins plus c-Myc. The authors used doxycycline as a switch to activate the genetic instructions.

For OSK, they used two AAV vectors, viral carriers of genetic instructions. One carried instructions for the three proteins; the other carried instructions for rtTA, a protein that switches on those instructions in the presence of doxycycline.

For OSKM, the second AAV carried instructions for both rtTA and c-Myc. This meant that c-Myc could be activated in a cell that received only this vector. Deigin described this possibility in the thread; the AAV constructs are specified in the paper’s methods.

The comparison combines two differences: the proteins in each set and the combinations of genetic instructions that individual cells could receive. An experiment that measures how often both AAV vectors enter the same cell, or uses the same co-delivery scheme in both groups, would allow the contribution of c-Myc to be measured.