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Related Concept Videos

Genetic Screens02:46

Genetic Screens

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Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
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Related Experiment Video

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High-throughput Functional Screening using a Homemade Dual-glow Luciferase Assay
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Proof-of-Concept of a DNA-Based Recording System for High-Throughput Functional Gene Screening.

Shoichi Kato1,2, Atsushi Ikemoto1,2, Jun Isayama1,2

  • 1JSR Corporation, Minato-ku, Tokyo 105-8640, Japan.

ACS Synthetic Biology
|April 15, 2026
PubMed
Summary
This summary is machine-generated.

We developed Perturbation-induced Intracellular Events Recorder (PiER), a novel pooled screening technology. PiER simplifies genetic screening by recording gene perturbation and pathway responses directly in DNA, enabling scalable functional genomics and drug discovery.

Keywords:
Cell signaling reporterDNA recordingFunctional genomicsPooled shRNA screeningSite-specific recombinaseWNT/β-catenin signaling

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Area of Science:

  • Molecular Biology
  • Genomics
  • Biotechnology

Background:

  • Pooled genetic screening is crucial for causal analyses but requires cost and handling improvements.
  • Existing methods often necessitate complex procedures like single-cell isolation or sorting.

Purpose of the Study:

  • To introduce Perturbation-induced Intracellular Events Recorder (PiER), a novel pooled screening technology.
  • To enable simpler, cost-effective, and scalable genetic screening by coupling gene perturbation with in situ signal recording.

Main Methods:

  • PiER utilizes a three-domain DNA architecture: Perturbation, Response, and Recorder.
  • The Response domain expresses a recombinase upon pathway activation, rewriting the Recorder domain to store perturbation-response histories.
  • Next-generation sequencing is used to read out perturbation and response histories from bulk DNA.

Main Results:

  • Demonstrated dose-dependent recombination in HEK293 cells using WNT-responsive constructs, validated by fluorescent reporters and qPCR.
  • Showcased stimulus-dependent recombination with a cAMP/CREB-responsive pilot vector.
  • Successfully identified WNT-related candidates using a pooled shRNA PiER library delivered via lentivirus.

Conclusions:

  • PiER offers a versatile and scalable platform for functional genomics.
  • This technology facilitates efficient drug-target discovery by simplifying pooled genetic screening.
  • PiER eliminates the need for single-cell isolation, sorting, or survival selection.