Person:
Tao, Yong

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Tao

First Name

Yong

Name

Tao, Yong

Filters

2015 - 20162

Settings

Author's Publications: search.filters.isAuthorOfPublication.6a0e2aa6-8c0e-4ba1-9d3e-d9054373f290

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Discovery and characterization of a peptide that enhances endosomal escape of delivered proteins in vitro and in vivo
    (American Chemical Society (ACS), 2015) Li, Margie; Tao, Yong; Shu, Yilai; LaRochelle, Jonathan R.; Steinauer, Angela; Thompson, David; Schepartz, Alanna; Chen, Zheng-Yi; Liu, David
    The in efficient delivery of proteins into mammalian cells remains a major barrier to realizing the therapeutic potential of many proteins. We and others have previously shown that superpositively charged proteins are efficiently endocytosed and can bring associated proteins and nucleic acids into cells. The vast majority of cargo delivered in this manner, however, remains in endosomes and does not reach the cytosol. In this study we designed and implemented a screen to discover peptides that enhance the endosomal escape of proteins fused to superpositively charged GFP (+36 GFP). From a screen of peptides previously reported to disrupt microbial membranes without known mammalian cell toxicity, we discovered a 13-residue peptide, aurein 1.2, that substantially increases cytosolic protein delivery by up to ~5-fold in a cytosolic fractionation assay in cultured cells. Four additional independent assays for non-endosomal protein delivery collectively suggest that aurein 1.2 enhances endosomal escape of associated endocytosed protein cargo. Structure-function studies clarified peptide sequence and protein conjugation requirements for endosomal escape activity. When applied to the in vivo delivery of +36 GFP–Crerecombinase fusions into the inner ear of live mice, fusion with aurein 1.2 dramatically increased non-endosomal Crerecombinase delivery potency, resulting in up to 100% recombined inner hair cellsand 96% recombined outer hair cells, compared to 0-4% recombined hair cells from +36-GFP- Cre without aurein 1.2. Collectively, these findings describe a genetically encodable, endosome escape-enhancing peptide that can substantially increase the cytoplasmic delivery of cationic proteins in vitro and in vivo.
  • Thumbnail Image
    Publication
    Adenovirus Vectors Target Several Cell Subtypes of Mammalian Inner Ear In Vivo
    (Hindawi Publishing Corporation, 2016) Shu, Yilai; Tao, Yong; Li, Wenyan; Shen, Jun; Wang, Zhengmin; Chen, Zheng-Yi
    Mammalian inner ear harbors diverse cell types that are essential for hearing and balance. Adenovirus is one of the major vectors to deliver genes into the inner ear for functional studies and hair cell regeneration. To identify adenovirus vectors that target specific cell subtypes in the inner ear, we studied three adenovirus vectors, carrying a reporter gene encoding green fluorescent protein (GFP) from two vendors or with a genome editing gene Cre recombinase (Cre), by injection into postnatal days 0 (P0) and 4 (P4) mouse cochlea through scala media by cochleostomy in vivo. We found three adenovirus vectors transduced mouse inner ear cells with different specificities and expression levels, depending on the type of adenoviral vectors and the age of mice. The most frequently targeted region was the cochlear sensory epithelium, including auditory hair cells and supporting cells. Adenovirus with GFP transduced utricular supporting cells as well. This study shows that adenovirus vectors are capable of efficiently and specifically transducing different cell types in the mammalian inner ear and provides useful tools to study inner ear gene function and to evaluate gene therapy to treat hearing loss and vestibular dysfunction.