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CRISPR

CRISPR

Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...

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Related Experiment Video

Updated: Apr 11, 2026

Genome Editing and Directed Differentiation of hPSCs for Interrogating Lineage Determinants in Human Pancreatic Development

Genome Editing and Directed Differentiation of hPSCs for Interrogating Lineage Determinants in Human Pancreatic Development

Published on: March 5, 2017

Mapping multimodal phenotypes to perturbations in cells and tissue with CRISPRmap.

Jiacheng Gu¹, Abhishek Iyer¹, Ben Wesley¹

¹Department of Biological Sciences, Columbia University, New York, NY, USA.

Nature Biotechnology

|October 7, 2024

Summary

CRISPRmap is a new optical pooled screening method that analyzes spatial phenotypes and genetic perturbations without cell lysis. This advanced technique identifies pathogenic mutations in cancer cells, improving treatment strategies.

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Determining the Role of Maternally-Expressed Genes in Early Development with Maternal Crispants

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Published on: December 21, 2021

Area of Science:

Genomics
Cell Biology
Biotechnology

Background:

Traditional sequencing methods for genetic screens require cell lysis, limiting the analysis of spatial phenotypes.
Optical pooled genetic screens offer a way to study cellular responses, including morphology and tissue organization, to genetic perturbations.
Investigating spatial phenotypes in diverse cell types and in vivo contexts remains challenging.

Purpose of the Study:

To develop a multimodal optical pooled CRISPR screening method for in situ barcode readout.
To enable the analysis of spatial phenotypes in challenging cell types and in vivo contexts.
To apply the method to identify pathogenic mutations affecting cancer therapy response.

Main Methods:

CRISPRmap combines in situ CRISPR guide-identifying barcode readout with multiplexed immunofluorescence and RNA detection.
Barcode detection is enhanced through combinatorial hybridization of DNA oligos.
The method allows for in situ readout in various cell types, including primary cells, stem cells, neurons, and in vivo tissues.

Main Results:

CRISPRmap successfully enabled in situ barcode readout in previously inaccessible cell types and contexts.
A screen in breast cancer cells revealed the effects of DNA damage repair gene variants on cellular responses to cancer therapies.
Optical phenotyping using CRISPRmap identified likely pathogenic patient-derived mutations previously classified as variants of unknown clinical significance.

Conclusions:

CRISPRmap is a powerful multimodal screening platform for in situ genetic perturbation analysis.
The method expands the applicability of optical pooled screening to diverse biological systems.
CRISPRmap has clinical relevance in identifying pathogenic mutations for improved cancer therapy selection.