Evidence map›Paper›PMID 24837679›Full record

ArticleMolecular cell2014

Multiplexed and programmable regulation of gene networks with an integrated RNA and CRISPR/Cas toolkit in human cells.

Lior Nissim, Samuel D Perli, Alexandra Fridkin, Pablo Perez-Pinera, Timothy K Lu

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 231 papers.

0numbers the graph read from it
0cells of the map it votes in
231citing papers in PubMed
24.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

231 citing papers in PubMed, 450 citations in OpenAlex.

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171 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Lior NissimSynthetic Biology Group, Research Laboratory of Electronics, Department of Biological Engineering and Electrical Engineering & Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Samuel D PerliSynthetic Biology Group, Research Laboratory of Electronics, Department of Biological Engineering and Electrical Engineering & Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Alexandra FridkinSynthetic Biology Group, Research Laboratory of Electronics, Department of Biological Engineering and Electrical Engineering & Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Pablo Perez-PineraSynthetic Biology Group, Research Laboratory of Electronics, Department of Biological Engineering and Electrical Engineering & Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Timothy K LuSynthetic Biology Group, Research Laboratory of Electronics, Department of Biological Engineering and Electrical Engineering & Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: timlu@mit.edu.
Massachusetts Institute of Technology · US

Funding

MIT Center for Integrative Synthetic BiologyP50GM098792 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WEISS, RON · 2013 to 2017
$11.0M
High-Throughput Nanoscale Approaches to Studying and Inhibiting Amyloid ToxicityDP2OD008435 · OD · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LU, TIMOTHY · 2011 to 2011
$2.4M
NIGMS NIH HHS P50 GM098792NIH HHS DP2 OD008435NIH HHS DP2OD008435
6 · The paper itself

Abstract

RNA-based regulation and CRISPR/Cas transcription factors (CRISPR-TFs) have the potential to be integrated for the tunable modulation of gene networks. A major limitation of this methodology is that guide RNAs (gRNAs) for CRISPR-TFs can only be expressed from RNA polymerase III promoters in human cells, limiting their use for conditional gene regulation. We present new strategies that enable expression of functional gRNAs from RNA polymerase II promoters and multiplexed production of proteins and gRNAs from a single transcript in human cells. We use multiple RNA regulatory strategies, including RNA-triple-helix structures, introns, microRNAs, and ribozymes, with Cas9-based CRISPR-TFs and Cas6/Csy4-based RNA processing. Using these tools, we efficiently modulate endogenous promoters and implement tunable synthetic circuits, including multistage cascades and RNA-dependent networks that can be rewired with Csy4 to achieve complex behaviors. This toolkit can be used for programming scalable gene circuits and perturbing endogenous networks for biology, therapeutic, and synthetic biology applications.

Indexed as

CRISPR-Cas SystemsGene Expression RegulationGene Regulatory NetworksHEK293 CellsHumansIntronsMicroRNAsPromoter Regions, GeneticRNA, CatalyticRNA Polymerase IIRNA, Small UntranslatedSynthetic BiologyTranscription FactorsMicroRNAsRNA, CatalyticRNA Polymerase IIRNA, Small UntranslatedTranscription Factors

Identifiers

PMID24837679
PMCPMC4077618
OpenAlexW2028543816

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.