Evidence map›Paper›PMID 27773616›Full record

ArticleMolecular plant2016

Compartmentalized Metabolic Engineering for Artemisinin Biosynthesis and Effective Malaria Treatment by Oral Delivery of Plant Cells.

Karan Malhotra, Mayavan Subramaniyan, Khushboo Rawat, Md Kalamuddin, M Irfan Qureshi, Pawan Malhotra, Asif Mohmmed, Katrina Cornish, Henry Daniell, Shashi Kumar

Open access · bronzeAbstract read
In one paragraph

Article in Molecular plant, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

48 citing papers in PubMed, 108 citations in OpenAlex.

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  3. NPlant biotechnology journal · 2025
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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

10 authors at 4 institutions in 2 countries.

Karan MalhotraMetabolic Engineering Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Mayavan SubramaniyanMetabolic Engineering Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Khushboo RawatMalaria Research Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Md KalamuddinMalaria Research Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
M Irfan QureshiDepartment of Biotechnology, Jamia Millia Islamia, New Delhi 110025, India.
Pawan MalhotraMalaria Research Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Asif MohmmedMalaria Research Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Katrina CornishDepartment of Horticulture and Crop Science, The Ohio State University, Wooster, OH 44691, USA.
Henry DaniellDepartment of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Shashi KumarMetabolic Engineering Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India. Electronic address: skrhode@icgeb.res.in.
International Centre for Genetic Engineering and Biotechnology · INDepartment of Biotechnology · INThe Ohio State University · USUniversity of Pennsylvania · US

Funding

Oral immune modulatory therapy using antigens bioencapsulated in plant cellsR01HL107904 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI DANIELL, HENRY · 2011 to 2023
$7.5M
Oral Therapy for Hemophilia AR01HL109442 · NHLBI · UNIVERSITY OF FLORIDA · PI DANIELL, HENRY, HERZOG, ROLAND W. · 2011 to 2015
$3.5M
Expression of Human Therapeutic Proteins in Transgenic Tobacco ChloroplastsR01GM063879 · NIGMS · UNIVERSITY OF CENTRAL FLORIDA · PI DANIELL, HENRY · 2002 to 2010
$2.0M
Oral therapy for diabetic retinopathy using ACE2/Ang1-7 bioencapsulated in plant cellsR01EY024564 · NEI · UNIVERSITY OF FLORIDA · PI DANIELL, HENRY, LI, QIUHONG · 2015 to 2018
$1.6M
NEI NIH HHS R01 EY024564NHLBI NIH HHS R01 HL107904NHLBI NIH HHS R01 HL109442NIGMS NIH HHS R01 GM063879
6 · The paper itself

Abstract

Artemisinin is highly effective against drug-resistant malarial parasites, which affects nearly half of the global population and kills >500 000 people each year. The primary cost of artemisinin is the very expensive process used to extract and purify the drug from Artemisia annua. Elimination of this apparently unnecessary step will make this potent antimalarial drug affordable to the global population living in endemic regions. Here we reported the oral delivery of a non-protein drug artemisinin biosynthesized (∼0.8 mg/g dry weight) at clinically meaningful levels in tobacco by engineering two metabolic pathways targeted to three different cellular compartments (chloroplast, nucleus, and mitochondria). The doubly transgenic lines showed a three-fold enhancement of isopentenyl pyrophosphate, and targeting AACPR, DBR2, and CYP71AV1 to chloroplasts resulted in higher expression and an efficient photo-oxidation of dihydroartemisinic acid to artemisinin. Partially purified extracts from the leaves of transgenic tobacco plants inhibited in vitro growth progression of Plasmodium falciparum-infected red blood cells. Oral feeding of whole intact plant cells bioencapsulating the artemisinin reduced the parasitemia levels in challenged mice in comparison with commercial drug. Such novel synergistic approaches should facilitate low-cost production and delivery of artemisinin and other drugs through metabolic engineering of edible plants.

Indexed as

Metabolic EngineeringAdministration, OralAnimalsArtemisininsChloroplastsMalaria, FalciparumMicePlant CellsPlants, Genetically ModifiedartemisininArtemisininsbioencapsulationdihydroartemisinic aciddrug biosynthesisisopentenyl pyrophosphateoral delivery of plant materialplant transformation

Identifiers

PMID27773616
PMCPMC5980236
OpenAlexW2538786612

What OpenQuestion holds

Textmetadata
LicenceTDM
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.