Evidence map›Paper›PMID 30840913›Full record

ArticleCell metabolism2019

Improving Drug Discovery by Nucleic Acid Delivery in Engineered Human Microlivers.

Liliana Mancio-Silva, Heather E Fleming, Alex B Miller, Stuart Milstein, Abigail Liebow, Patrick Haslett, Laura Sepp-Lorenzino, Sangeeta N Bhatia

Abstract read
In one paragraph

Article in Cell metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Profile of Sangeeta Bhatia.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  5. Review
  6. Article
  7. Review
  8. Review
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

8 authors.

Liliana Mancio-SilvaInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Heather E FlemingInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Alex B MillerInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Broad Institute, Cambridge, MA 02142, USA.
Stuart MilsteinAlnylam Pharmaceuticals, 300 3rd Street, Cambridge, MA 02142, USA.
Abigail LiebowAlnylam Pharmaceuticals, 300 3rd Street, Cambridge, MA 02142, USA.
Patrick HaslettAlnylam Pharmaceuticals, 300 3rd Street, Cambridge, MA 02142, USA.
Laura Sepp-LorenzinoAlnylam Pharmaceuticals, 300 3rd Street, Cambridge, MA 02142, USA.
Sangeeta N BhatiaInstitute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Broad Institute, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA 02142, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: sbhatia@mit.edu.

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Paula T Hammond · 1985 to 2026
$93.9M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA014051
6 · The paper itself

Abstract

The liver plays a central role in metabolism; however, xenobiotic metabolism variations between human hepatocytes and those in model organisms create challenges in establishing functional test beds to detect the potential drug toxicity and efficacy of candidate small molecules. In the emerging areas of RNA interference, viral gene therapy, and genome editing, more robust, long-lasting, and predictive human liver models may accelerate progress. Here, we apply a new modality to a previously established, functionally stable, multi-well bioengineered microliver-fabricated from primary human hepatocytes and supportive stromal cells-in order to advance both small molecule and nucleic acid therapeutic pipelines. Specifically, we achieve robust and durable gene silencing in vitro to tune the human metabolism of small molecules, and demonstrate its capacity to query the potential efficacy and/or toxicity of candidate therapeutics. Additionally, we apply this engineered platform to test siRNAs designed to target hepatocytes and impact human liver genetic and infectious diseases.

Indexed as

RNA Interference3T3 CellsAnimalsDrug DiscoveryHepatocytesHumansLiverMicePlasmodium falciparumRNA, Small InterferingStromal CellsRNA, Small Interferingdrug metabolismlivermalariamicropatterningnucleic acid therapiesPlasmodium falciparumprimary human hepatocytessiRNA

Identifiers

PMID30840913
PMCPMC6408324

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.