ABSTRACT
Experimental cell models are indispensable for clarifying the pathophysiology of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and for developing therapeutic agents. To recapitulate the symptoms and drug response of COVID-19 patients in vitro, SARS-CoV-2 studies using physiologically relevant human embryonic stem (ES)/induced pluripotent stem (iPS) cell-derived somatic cells and organoids are ongoing. These cells and organoids have been used to show that SARS-CoV-2 can infect and damage various organs including the lung, heart, brain, intestinal tract, kidney, and pancreas. They are also being used to develop COVID-19 therapeutic agents, including evaluation of their antiviral efficacy and safety. The relationship between COVID-19 aggravation and human genetic backgrounds has been investigated using genetically modified ES/iPS cells and patient-derived iPS cells. This review summarizes the latest results and issues of SARS-CoV-2 research using human ES/iPS cell-derived somatic cells and organoids.
Subject(s)
COVID-19 , Human Embryonic Stem Cells/physiology , Organoids/physiology , SARS-CoV-2/physiology , Biomedical Research/methods , Biomedical Research/trends , COVID-19/etiology , COVID-19/pathology , COVID-19/therapy , Genetic Therapy/methods , Genetic Therapy/trends , Human Embryonic Stem Cells/transplantation , Humans , Induced Pluripotent Stem Cells/physiology , Induced Pluripotent Stem Cells/transplantation , Organoids/cytology , Organoids/transplantationABSTRACT
Human-induced pluripotent stem cells (hiPSCs) and CRISPR/Cas9 gene editing system represent two instruments of basic and translational research, which both allow to acquire deep insight about the molecular bases of many diseases but also to develop pharmacological research.This review is focused to draw up the latest technique of gene editing applied on hiPSCs, exploiting some of the genetic manipulation directed to the discovery of innovative therapeutic strategies. There are many expediencies provided by the use of hiPSCs, which can represent a disease model clinically relevant and predictive, with a great potential if associated to CRISPR/Cas9 technology, a gene editing tool powered by ease and precision never seen before.Here, we describe the possible applications of CRISPR/Cas9 to hiPSCs: from drug development to drug screening and from gene therapy to the induction of the immunological response to specific virus infection, such as HIV and SARS-Cov-2.