CRISPR Single-Cell Screening Drives Biological Discovery

Genomic analyses are yielding a host of new information on the multiple genetic abnormalities associated with specific types of cancer. A comprehensive description of cancer-associated genetic abnormalities can improve our ability to classify tumors into clinically relevant subgroups and sometimes identify drivers. However, the functional significance of cancer-associated mutations is often difficult to discern. Forward genetic screens provide a powerful tool to identify genes or genetic networks that contribute to specific biological phenotypes or diseases and therefore hold great potential for elucidating gene function and revealing therapeutic targets for diseases. The advent of CRISPR-Cas technology has revolutionized genome editing in higher eukaryotes and enables efficient gene manipulation in mammalian cells. CRISPR guide-RNA libraries allow facile generation of a pool of genetically perturbed cells and its application in genetic screens has marked a major breakthrough for functional genomics in mammalian cells.

Single cell analysis, starting with the earliest low parameter fluorescent experiments, helped define the major cell subsets of human cellular systems as we understand them today. Now, a novel combination of single cell analysis and metal isotopes based mass spectrometry (MIBI) offers a routine examination of 30+ parameters at the nanometer scale, without the interference of spectral overlap characteristic of fluorescent reporters. With this platform, we have reached new levels of organizational understanding in human pathobiology – especially when combined with novel single-cell visualization and analysis methods.

There are approximately 7,000 distinct rare diseases affecting 350 million people worldwide, approximately 80 percent of which are caused by faulty genes. The US Food and Drug Administration (FDA) has more than 700 active Investigational New Drug Applications (INDs) for gene and cell therapies and in 2017, the FDA approved two cell-based gene therapies and it is anticipated that gene therapy will become a mainstay treatment for many rare diseases.

What is DNA and how can learning about yours help you to build your family tree? Discover the ins and outs of DNA including: Components and Types of DNA, How DNA replicates itself, Mutations, Genes and Chromosomes, Dominant and Recessive genes, Sex-linked genes, Hereditary Diseases, Inheritance of blood types.