Direct Functional Protein Delivery with a Peptide into Neonatal and Adult Mammalian Inner Ear In Vivo

Kun Zhang, Xiaoting Cheng, Liping Zhao, Mingqian Huang, Yong Tao, Hongbo Zhang, Jessica Rosenholm, Min Zhuang, Zheng-Yi Chen, Bing Chen, Yilai Shu

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Sammanfattning

The aim of this study was to study an antimicrobial peptide (AMP), aurein 1.2, which substantially increased protein delivery directly into multiple mammalian inner-ear cell types in vivo. Different concentrations of aurein 1.2 with superpositively charged GFP (+36 GFP) protein fused with Cre recombinase were delivered to postnatal day 1-2 (P1-2) and adult cochleae of Cre reporter transgenic mice with various delivery methods. By cochleostomy at different concentrations of aurein 1.2–+36 GFP (1 μM, 5 μM, 22.5 μM, and 50 μM, respectively), the tdTomato (tdT) expression was observed in outer hair cells (OHCs; 20.77%, 23.02%, 76.36%, and 92.47%, respectively) and inner hair cells (IHCs; 14.90%, 44.50%, 89.59%, and 96.13%, respectively) in the cochlea. The optimal concentration was 22.5 μM with the highest transfection efficiency and the lowest cytotoxicity. Wide-spread tdT signals were detected in the cochlear-supporting cells, utricular-supporting cells, auditory nerve, and spiral ligament in neonatal and adult mice. Compared to cochleostomy, injection through the round window membrane (RWM) also produced highly efficient tdT+ labeled cells with less cell loss. In summary, the peptide aurein 1.2 fused with +36 GFP dramatically expanded the target cells with increased efficiency in direct protein delivery in the inner ear. Aurein 1.2–+36 GFP has the potential to be developed as protein-based therapy in regeneration and genome editing in the mammalian inner ear.
OriginalspråkEngelska
Sidor (från-till)511-519
TidskriftMolecular Therapy - Methods & Clinical Development
Volym18
Utgåva11
DOI
StatusPublicerad - sep 2020
MoE-publikationstypA1 Tidskriftsartikel-refererad

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