A high affinity kidney targeting by chitobionic acid-conjugated polysorbitol gene transporter alleviates unilateral ureteral obstruction in rats.
Aside from kidney transplantation - a procedure which is exceedingly dependent on donor-match and availability leading to excessive costs - there are currently no permanent treatments available which reverse kidney injury and failure. However, kidney-specific targeted gene therapy has outstanding potential to treat kidney-related dysfunction. Herein we report a novel kidney-specific targeted gene delivery system developed through the conjugation of chitobionic acid (CBA) to a polysorbitol gene transporter (PSGT) synthesized from sorbitol diacrylate and low molecular weight polyethylenimine (PEI) carrying hepatocyte growth factor (HGF) gene to alleviate unilateral ureteral obstruction (UUO) in rats. CBA-PSGT performed exceptionally well for targeted delivery of HGF to kidney tissues compared to its non-targeted counterparts (P < 0.001) after systemic tail-vein injection and significantly reduced the UUO symptoms, returning the UUO rats to a normal health status. The kidney-targeted CBA-PSGT-delivered HGF also strikingly reduced various pathologic and molecular markers in vivo such as the level of collagens (type I and II), blood urea nitrogen (BUN), creatinine, and the expressions of ICAM-1, TIMP-1 and α-SMA which play a critical role in obstructive kidney functions. Therefore, CBA-PSGT should be further investigated because of its potential to alleviate UUO and kidney-related diseases using high affinity kidney targeting.
Brigham and Women's Hospital & Harvard Medical School, Boston, MA 02115, USA; Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Mohammad Ariful
MA
Islam
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea; Graduate Group of Tumor Biology, Seoul National University, Seoul 03080, Republic of Korea.
Sanghwa
S
Kim
Brigham and Women's Hospital & Harvard Medical School, Boston, MA 02115, USA; Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Jannatul
J
Firdous
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
Ah-Young
AY
Lee
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
Seong-Ho
SH
Hong
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
Min Kyeong
MK
Seo
Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea; Wyss Institute for Biologically Inspired Engineering, Harvard Medical School, Boston, MA 02115, USA.
Tae-Eun
TE
Park
Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Cheol-Heui
CH
Yun
Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Yun-Jaie
YJ
Choi
Laboratory of Pathology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
Chanhee
C
Chae
Department of Agricultural Biotechnology & Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: chocs@snu.ac.kr.
Chong-Su
CS
Cho
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea; Graduate School of Convergence Science and Technology, Suwon 16229, Republic of Korea; Graduate Group of Tumor Biology, Seoul National University, Seoul 03080, Republic of Korea; Advanced Institute of Convergence Technology, Seoul National University, Suwon 16229, Republic of Korea; Institute of GreenBio Science Technology, Seoul National University, Pyeongchang 25354, Republic of Korea. Electronic address: mchotox@snu.ac.kr.
Myung-Haing
MH
Cho
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004187:Disaccharides / Q000737:chemistry*; D018014:Gene Transfer Techniques; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D011094:Polyethyleneimine / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013012:Sorbitol / Q000031:analogs & derivatives*; D013400:Sugar Acids / Q000737:chemistry*; D014517:Ureteral Obstruction / Q000235:genetics / Q000473:pathology / Q000628:therapy*
D004187:Disaccharides; D013400:Sugar Acids; C000625576:chitobionic acid; D013012:Sorbitol; D017228:Hepatocyte Growth Factor; D011094:Polyethyleneimine; D004247:DNA
Chitobionic acid; HGF; Kidney targeting; Polysorbitol gene transporter; UUO