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Related Concept Videos

CRISPR01:59

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 Short...
CRISPR01:59

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 Short...

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Related Experiment Video

Updated: Jun 13, 2026

Pooled CRISPR-Based Genetic Screens in Mammalian Cells
09:05

Pooled CRISPR-Based Genetic Screens in Mammalian Cells

Published on: September 4, 2019

Large-scale, spatially resolved panoramic CRISPR screening in native tissue environments using Perturb-DBiT.

Alev Baysoy1, Xiaolong Tian1,2, Paul Renauer2

  • 1Department of Biomedical Engineering, Yale University, New Haven, CT, USA.

Nature Biotechnology
|June 11, 2026
PubMed
Summary

Perturb-DBiT enables large-scale, spatially resolved CRISPR screening in situ. This method links genetic perturbations to complex biological processes like cancer metastasis and immune response.

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Last Updated: Jun 13, 2026

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Published on: November 2, 2020

Area of Science:

  • Molecular Biology
  • Genomics
  • Cancer Research

Background:

  • Spatially resolved in vivo CRISPR screening is limited in scale and scope.
  • Current methods cannot comprehensively analyze perturbations in complex tissues.

Purpose of the Study:

  • To develop a novel method for large-scale, spatially resolved CRISPR screening in situ.
  • To investigate the impact of genetic perturbations on cancer metastasis and the tumor immune microenvironment.

Main Methods:

  • Developed Perturb-DBiT for co-sequencing of spatial total RNA and single guide RNAs (sgRNAs) in situ.
  • Applied large sgRNA panels (80,000+) to human cancer metastatic models and immune-competent mouse models.
  • Integrated transcriptional pseudotime trajectories to analyze clonal dynamics.

Main Results:

  • Linked perturbations in long noncoding RNAs, microRNAs, and tRNAs to tumor migration and growth.
  • Observed significant impacts of perturbations on clonal dynamics and cooperation.
  • Identified distinct synergistic effects on immune infiltration and suppression in the tumor microenvironment.

Conclusions:

  • Perturb-DBiT offers a comprehensive, spatially resolved view of perturbation responses in complex tissues.
  • The method facilitates understanding of small and large RNA regulation, tumor progression, and immune interactions.