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In vivo uterine local gene delivery system using TAT‐displaying bionanocapsules
Author(s) -
Koizumi Kaori,
Nakamura Hitomi,
Iijima Masumi,
Matsuzaki Takashi,
Somiya Masaharu,
Kumasawa Keiichi,
Kimura Tadashi,
Kuroda Shun'ichi
Publication year - 2019
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.3140
Subject(s) - uterus , immunogen , gene delivery , microbiology and biotechnology , antibody , genetic enhancement , biology , in utero , andrology , gene , monoclonal antibody , chemistry , medicine , immunology , endocrinology , fetus , pregnancy , biochemistry , genetics
Background The uterus is an organ that is directly accessible via the transvaginal route, whereas the drug delivery system and the gene delivery system (GDS) for the uterus are very limited, even in animal models. In the present study, we optimized a bionanocapsule (BNC) comprising a hepatitis B virus envelope L‐protein particle, for which a structurally similar particle has been used as an immunogen of a conventional HB vaccine worldwide for more than 30 years, as a local uterine GDS using a mouse model. Methods To display various antibodies for re‐targeting to different cells other than hepatic cells, the pre‐S1 region of BNC was replaced with a tandem form of the protein A‐derived immunoglobulin G Fc‐interacting region (Z domain, ZZ‐BNC). To induce strong cell adhesion after local administration into the uterine cavity, ZZ‐BNC was modified with a transactivator of transcription (TAT) peptide. Results Gene transfer using TAT‐modified ZZ‐BNC is approximately 5000‐ or 18‐fold more efficient than the introduction of the same dose of naked DNAs or the use of the cationic liposomes, respectively. TAT‐modified ZZ‐BNC was rapidly eliminated from the uterus and had no effect on the pregnancy rate, litter size or fetal growth. Conclusions TAT‐modified ZZ‐BNC could be a useful GDS for uterine endometrial therapy via local uterine injection.