ArticleBiochimica et biophysica acta2011
A HA2-Fusion tag limits the endosomal release of its protein cargo despite causing endosomal lysis.
Article in Biochimica et biophysica acta, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 45 citations in OpenAlex.
- Comparison of Cell-Penetrating and Fusogenic TAT-HA2 Peptide Performance in Peptideplex, Multicomponent, and Conjugate siRNA Delivery Systems.ACS omega · 2024Article
- Charge-guided masking of a membrane-destabilizing peptide enables efficient endosomal escape for targeted intracellular delivery of proteins.Acta pharmaceutica Sinica. B · 2024Article
- Cell-Penetrating Peptide-Mediated Biomolecule Transportation in Artificial Lipid Vesicles and Living Cells.Molecules (Basel, Switzerland) · 2024Review
- Cell-Penetrating and Targeted Peptides Delivery Systems as Potential Pharmaceutical Carriers for Enhanced Delivery across the Blood-Brain Barrier (BBB).Pharmaceutics · 2023Review
- Nanoparticles for vaccine and gene therapy: Overcoming the barriers to nucleic acid delivery.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2022Review
- The role of cell-penetrating peptides in potential anti-cancer therapy.Clinical and translational medicine · 2022Review
- Nanolipoprotein-Mediated Her2 Protein Transfection Induces Malignant Transformation in Human Breast Acinar Cultures.ACS omega · 2021Article
- Efficient intracellular delivery of proteins by a multifunctional chimaeric peptide in vitro and in vivo.Nature communications · 2021Article
- Novel pH Selective, Highly Lytic Peptides Based on a Chimeric Influenza Hemagglutinin Peptide/Cell Penetrating Peptide Motif.Molecules (Basel, Switzerland) · 2019Article
- Cell-penetrating peptide sequence and modification dependent uptake and subcellular distribution of green florescent protein in different cell lines.Scientific reports · 2019Article
- Trapped! A Critical Evaluation of Methods for Measuring Total Cellular Uptake versus Cytosolic Localization.Bioconjugate chemistry · 2019Review
- Endosomal Escape and Cytosolic Penetration of Macromolecules Mediated by Synthetic Delivery Agents.Bioconjugate chemistry · 2019Review
- Current Development of siRNA Bioconjugates: From Research to the Clinic.Frontiers in pharmacology · 2019Review
- A platform for discovery of functional cell-penetrating peptides for efficient multi-cargo intracellular delivery.Scientific reports · 2018Article
- Efficient Delivery of Macromolecules into Human Cells by Improving the Endosomal Escape Activity of Cell-Penetrating Peptides: Lessons Learned from dfTAT and its Analogs.Biomolecules · 2018Review
- Article
- TAT and HA2 facilitate cellular uptake of gold nanoparticles but do not lead to cytosolic localisation.PloS one · 2015Article
- Improving the endosomal escape of cell-penetrating peptides and their cargos: strategies and challenges.Pharmaceuticals (Basel, Switzerland) · 2012Review
- Protein transduction in human cells is enhanced by cell-penetrating peptides fused with an endosomolytic HA2 sequence.Peptides · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundProtein transduction domains (PTDs) can be fused to a protein to render it cell-permeable. The delivery efficiencies of PTDs are, however, often poor because PTD-protein conjugates cannot escape from endosomes. A potential solution to this problem consists in adding HA2 analogs to the PTD-protein construct as these peptides can cause endosomal lysis upon acidification of the endosomal lumen. To date, however, the utility of HA2-based PTDs has not been clearly established.
methodsWe investigate the biophysical and cellular properties of the glutamate-rich HA2 analog E5 fused to the model protein TAT-mCherry.
resultsE5-TAT-mCherry causes the release of fluorescent dextrans trapped with the protein inside endosomes. Yet, E5-TAT-mCherry itself is not released in the cytosol of cells, indicating that the protein remained trapped inside endosomes even after endosomal lysis takes place. Cytosolic delivery of the protein could be achieved, however, by insertion of a disulfide bond between E5 and its cargo.
conclusionsThese results show that E5 causes the retention of its fused protein inside endosomes even after lysis takes place. GENERAL SIGNIFICANCE: These data establish that HA2 analogs might not be useful PTDs unless cleavable linkers are engineered between PTD and protein cargo.
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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.