Enhanced gene expression by a novel designed leucine zipper endosomolytic peptide
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A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
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International Journal of Pharmaceutics, Volume 601
Abstract
An endosomal trap is a major barrier in gene therapy. We have designed an endosomolytic peptide based on the leucine zipper sequence and characterized it both structurally and functionally. The results illustrated that leucine zipper endosomolytic peptide (LZEP) exhibited appreciable hemolysis of human red blood cells (hRBCs) at pH 5.0, but negligible hemolysis at pH 7.4. Calcein release experiment indicated that only at pH 5.0 but not at pH 7.4, LZEP was able to permeabilize hRBCs. LZEP revealed significant self-assembly as well as peptide induced α-helical structure at pH 5.0. Unlike at pH 5.0, LZEP failed to self-assemble and showed a random coil structure at pH 7.4. Transfection data depicted that lipoplexes modified with LZEP resulted in significantly higher gene expression as compared to lipoplexes without LZEP. Interestingly, the transfection efficacy of LZEP modified lipid nanoparticles reached the levels of Lipofectamine 2000 (LF 2000), without any cellular toxicity as observed by MTT assay. The results suggest a novel approach for designing endosomolytic peptides by employing the leucine zipper sequence and simultaneously the designed peptides could be utilized for enhancing gene delivery into mammalian cells.Description
Funding Information: This study was conducted in the European Community 6th framework program; contract NMP4-CT-2006-026556, NANOEAR, aimed at targeted drug & gene delivery into the cells of the inner ear. This work was also financially supported by the KR personal grant (project number 64814), which was financed by the Jane and Aatos Erkko Foundation. Funding Information: This paper is dedicated to the memory of the late Prof. Paavo Kinnunen. This study was conducted in the European Community 6th framework program; contract NMP4-CT-2006-026556, NANOEAR, aimed at targeted drug & gene delivery into the cells of the inner ear. This work was also financially supported by the KR personal grant (project number 64814), which was financed by the Jane and Aatos Erkko Foundation. Publisher Copyright: © 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
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Ahmad, A, Rilla, K, Zou, J, Zhang, W, Pyykkö, I, Kinnunen, P & Ranjan, S 2021, 'Enhanced gene expression by a novel designed leucine zipper endosomolytic peptide', International Journal of Pharmaceutics, vol. 601, 120556. https://doi.org/10.1016/j.ijpharm.2021.120556