Enhanced gene expression by a novel designed leucine zipper endosomolytic peptide

Aqeel Ahmad, Kirsi Rilla, Jing Zou, Weikai Zhang, Ilmari Pyykkö, Paavo Kinnunen, Sanjeev Ranjan*

*Corresponding author for this work

    Research output: Contribution to journalArticleScientificpeer-review

    2 Citations (Scopus)
    46 Downloads (Pure)


    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.

    Original languageEnglish
    Article number120556
    JournalInternational Journal of Pharmaceutics
    Publication statusPublished - 15 May 2021
    MoE publication typeA1 Journal article-refereed


    • Endosomal escape
    • Endosomolytic peptides
    • Gene delivery
    • Gene expression
    • Leucine zipper
    • Liposome nanoparticles.


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