Evidence map›Paper›PMID 30997751›Full record

ArticleAdvanced healthcare materials2019

TPP1 Delivery to Lysosomes with Extracellular Vesicles and their Enhanced Brain Distribution in the Animal Model of Batten Disease.

Matthew J Haney, Natalia L Klyachko, Emily B Harrison, Yuling Zhao, Alexander V Kabanov, Elena V Batrakova

Open access · greenAbstract read
In one paragraph

Article in Advanced healthcare materials, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed, 2 pooled it
5.2field-weighted citation impact, top 3% 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

89 citing papers in PubMed, 2 syntheses or guidelines pooled it, 146 citations in OpenAlex.

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  15. Recent advances in mucopolysaccharidosis IVA treatment.Orphanet journal of rare diseases · 2025
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29 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

6 authors at 1 institution in 3 countries.

Matthew J HaneyCenter for Nanotechnology in Drug Delivery and Carolina Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Natalia L KlyachkoCenter for Nanotechnology in Drug Delivery and Carolina Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Emily B HarrisonCenter for Nanotechnology in Drug Delivery and Carolina Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Yuling ZhaoCenter for Nanotechnology in Drug Delivery and Carolina Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Alexander V KabanovCenter for Nanotechnology in Drug Delivery and Carolina Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Elena V BatrakovaCenter for Nanotechnology in Drug Delivery and Carolina Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.ORCID 0000-0002-9386-3790
University of North Carolina at Chapel Hill · US

Funding

CAROLINA CANCER NANOTECHNOLOGY TRAINING PROGRAM (C-CNTP)T32CA196589 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Gaorav P. Gupta, ALEXANDER V KABANOV · 2015 to 2026
$4.5M
Cell-based Platform for Gene Delivery to the BrainR01NS102412 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BATRAKOVA, ELENA · 2018 to 2022
$1.7M
Eshelman Institute for Innovation EII UNC-29202NCI NIH HHS T32 CA196589NINDS NIH HHS R01 NS102412Russian Foundation for Basic Research 17-54-33027Russian Foundation for Basic Research 18-29-09154
6 · The paper itself

Abstract

Extracellular vesicles (EVs) are promising natural nanocarriers for delivery of various types of therapeutics. Earlier engineered EV-based formulations for neurodegenerative diseases and cancer are reported. Herein, the use of macrophage-derived EVs for brain delivery of a soluble lysosomal enzyme tripeptidyl peptidase-1, TPP1, to treat a lysosomal storage disorder, Neuronal Ceroid Lipofuscinoses 2 (CLN2) or Batten disease, is investigated. TPP1 is loaded into EVs using two methods: i) transfection of parental EV-producing macrophages with TPP1-encoding plasmid DNA (pDNA) or ii) incorporation therapeutic protein TPP1 into naive empty EVs. For the former approach, EVs released by pretransfected macrophages contain the active enzyme and TPP1-encoding pDNA. To achieve high loading efficiency by the latter approach, sonication or permeabilization of EV membranes with saponin is utilized. Both methods provide proficient incorporation of functional TPP1 into EVs (EV-TPP1). EVs significantly increase stability of TPP1 against protease degradation and provide efficient TPP1 delivery to target cells in in vitro model of CLN2. The majority of EV-TPP1 (≈70%) is delivered to target organelles, lysosomes. Finally, a robust brain accumulation of EV carriers and increased lifespan is recorded in late-infantile neuronal ceroid lipofuscinosis (LINCL) mouse model following intraperitoneal administration of EV-TPP1.

Indexed as

AminopeptidasesBrainDipeptidyl-Peptidases and Tripeptidyl-PeptidasesExtracellular VesiclesNeuronal Ceroid-LipofuscinosesSerine ProteasesAnimalsDisease Models, AnimalHumansLysosomesMicePC12 CellsRatsTripeptidyl-Peptidase 1AminopeptidasesDipeptidyl-Peptidases and Tripeptidyl-PeptidasesSerine ProteasesTPP1 protein, humanTpp1 protein, mouseTpp1 protein, ratTripeptidyl-Peptidase 1Batten diseasebraindrug delivery systemsEVslysosomal storage diseases

Identifiers

PMID30997751
PMCPMC6584948
OpenAlexW2939686995

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.