ArticleThe Journal of clinical investigation2006
TAT-mediated intracellular delivery of purine nucleoside phosphorylase corrects its deficiency in mice.
Article in The Journal of clinical investigation, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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.
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.
Who cites it
31 citing papers in PubMed, 75 citations in OpenAlex.
- Nrf2 activator peptide protects the brain from cerebral vascular dysfunction in alcohol ingestion.JCI insight · 2026Article
- HIV Tat as a latency reversing agent: turning the tables on viral persistence.Frontiers in immunology · 2025Review
- Spatially resolved metabolomics and isotope tracing reveal dynamic metabolic responses of dentate granule neurons with acute stimulation.Nature metabolism · 2023Article
- Spatially resolved metabolomics and isotope tracing reveal dynamic metabolic responses of dentate granule neurons with acute stimulation.Research square · 2023Article
- Inborn Errors of Purine Salvage and Catabolism.Metabolites · 2023Review
- Purine nucleoside phosphorylase deficiency induces p53-mediated intrinsic apoptosis in human induced pluripotent stem cell-derived neurons.Scientific reports · 2022Article
- Expression, Purification, Characterization and Cellular Uptake of MeCP2 Variants.The protein journal · 2022Article
- Identification of contributing genes of Huntington's disease by machine learning.BMC medical genomics · 2020Article
- Partial Purine Nucleoside Phosphorylase Deficiency Helps Determine Minimal Activity Required for Immune and Neurological Development.Frontiers in immunology · 2020Article
- Internalization mechanisms of cell-penetrating peptides.Beilstein journal of nanotechnology · 2020Review
- Review of Current Cell-Penetrating Antibody Developments for HIV-1 Therapy.Molecules (Basel, Switzerland) · 2018Review
- A cell-penetrating whole molecule antibody targeting intracellular HBx suppresses hepatitis B virus via TRIM21-dependent pathway.Theranostics · 2018Article
- Protein therapy using MafA fused to a polyarginine transduction domain attenuates glucose levels of streptozotocin‑induced diabetic mice.Molecular medicine reports · 2017Article
- Inhibition of regulated cell death by cell-penetrating peptides.Cellular and molecular life sciences : CMLS · 2016Review
- Fibrinogen-derived fibrinostatin inhibits tumor growth through anti-angiogenesis.Cancer science · 2015Article
- Inborn errors of metabolism underlying primary immunodeficiencies.Journal of clinical immunology · 2014Review
- Proteomic analysis of rat cartilage: the identification of differentially expressed proteins in the early stages of osteoarthritis.Proteome science · 2014Article
- Replacement of the C6ORF66 assembly factor (NDUFAF4) restores complex I activity in patient cells.Molecular medicine (Cambridge, Mass.) · 2013Article
- Molecular logistics using cytocleavable polyrotaxanes for the reactivation of enzymes delivered in living cells.Scientific reports · 2013Article
- Non-covalent ligand conjugation to biotinylated DNA nanoparticles using TAT peptide genetically fused to monovalent streptavidin.Journal of drug targeting · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defects in purine nucleoside phosphorylase (PNP) enzyme activity result in abnormal nucleoside homeostasis, severe T cell immunodeficiency, neurological dysfunction, and early death. Protein transduction domain (PTD) can transfer molecules into cells and may help restore PNP activity in cases of PNP deficiency. However, long-term use of PTD to replace enzymes in animal models or patients has not previously been described. We fused human PNP to the HIV-TAT PTD and found that the fusion with TAT changed the retention and distribution of PNP in PNP-deficient mice. TAT induced rapid intracellular delivery of PNP into tissues, including the brain, prevented urinary excretion of PNP, and protected PNP from neutralizing antibodies, resulting in significant extension of the enzyme's biological activity in vivo. Frequent TAT-PNP injections in PNP-deficient mice corrected the metabolic disorder and immune defects with no apparent toxicity. TAT-PNP remained effective over 24 weeks of treatment, resulting in continued improvement in immune function and extended survival. Our data demonstrate that TAT changes the properties of PNP in vivo and that long-term intracellular delivery of PNP by TAT corrects PNP deficiency in mice. We provide evidence to promote further use of PTD to treat diseases that require repeated intracellular enzyme or protein delivery.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.