In vivo CRISPR screening for key regulators in liver regeneration.

Upon intravenous delivery of lentiviral vectors to the Cas9LSL+/+Fah-/- animals, a portion of the hepatocytes will be expressing Fah and sgRNA(s) targeting certain gene(s). After NTBC withdrawal, the Fah-/- hepatocytes that have not received the lentiviral vectors will die shortly, whereas the hepatocytes that have successfully received the lentiviral vectors thus expressing Fah will survive and repopulate in vivo. We therefore can tell later in these repopulated cells the sgRNAs (hence the corresponding genes) that can likely confer liver cells a repopulation and regeneration advantage.