BACKGROUND: Previous studies showed that microRNA-29b (miR-29b) inhibits renal fibrosis. Therefore, miR-29b replacement therapy represents a promising approach for treating renal fibrosis. However, an efficient method of kidney-targeted miRNA delivery has yet to be established. Recombinant adeno-associated virus (rAAV) vectors have great potential for clinical application. For kidney-targeted gene delivery, the most suitable AAV serotype has yet to be established. Here, we identified the most suitable AAV serotype for kidney-targeted gene delivery and determined that AAV-mediated miR-29b delivery can suppress renal fibrosis in vivo. METHOD: To determine which AAV serotype is suitable for kidney cells, GFP-positive cells were identified by flow cytometry after the infection of rAAV serotype 1-9 vectors containing the EGFP gene. Next, we injected rAAV vectors into the renal pelvis to determine transduction efficiency in vivo. GFP expression was measured seven days after injecting rAAV serotype 1-9 vectors carrying the EGFP gene. Finally, we investigated whether rAAV6-mediated miR-29b delivery can suppress renal fibrosis in UUO mouse model. RESULTS: We found that rAAV6 vector is the most suitable for targeting kidney cells regardless of animal species in vitro and rAAV6 is the most suitable vector for kidney-targeted in vivo gene delivery in mice. Intra-renal pelvic injection of rAAV vectors can transduce genes into kidney TECs. Furthermore, rAAV6-mediated miR-29b delivery attenuated renal fibrosis in UUO model by suppressing Snail1 expression. CONCLUSION: Our study has revealed that rAAV6 is the most suitable serotype for kidney-targeted gene delivery and rAAV6-mediated miR-29b delivery into kidney TECs can suppress established renal fibrosis.
BACKGROUND: Previous studies showed that microRNA-29b (miR-29b) inhibits renal fibrosis. Therefore, miR-29b replacement therapy represents a promising approach for treating renal fibrosis. However, an efficient method of kidney-targeted miRNA delivery has yet to be established. Recombinant adeno-associated virus (rAAV) vectors have great potential for clinical application. For kidney-targeted gene delivery, the most suitable AAV serotype has yet to be established. Here, we identified the most suitable AAV serotype for kidney-targeted gene delivery and determined that AAV-mediated miR-29b delivery can suppress renal fibrosis in vivo. METHOD: To determine which AAV serotype is suitable for kidney cells, GFP-positive cells were identified by flow cytometry after the infection of rAAV serotype 1-9 vectors containing the EGFP gene. Next, we injected rAAV vectors into the renal pelvis to determine transduction efficiency in vivo. GFP expression was measured seven days after injecting rAAV serotype 1-9 vectors carrying the EGFP gene. Finally, we investigated whether rAAV6-mediated miR-29b delivery can suppress renal fibrosis in UUO mouse model. RESULTS: We found that rAAV6 vector is the most suitable for targeting kidney cells regardless of animal species in vitro and rAAV6 is the most suitable vector for kidney-targeted in vivo gene delivery in mice. Intra-renal pelvic injection of rAAV vectors can transduce genes into kidney TECs. Furthermore, rAAV6-mediated miR-29bdelivery attenuated renal fibrosis in UUO model by suppressing Snail1 expression. CONCLUSION: Our study has revealed that rAAV6 is the most suitable serotype for kidney-targeted gene delivery and rAAV6-mediated miR-29b delivery into kidney TECs can suppress established renal fibrosis.
Authors: K J Fisher; K Jooss; J Alston; Y Yang; S E Haecker; K High; R Pathak; S E Raper; J M Wilson Journal: Nat Med Date: 1997-03 Impact factor: 53.440
Authors: P D Kessler; G M Podsakoff; X Chen; S A McQuiston; P C Colosi; L A Matelis; G J Kurtzman; B J Byrne Journal: Proc Natl Acad Sci U S A Date: 1996-11-26 Impact factor: 11.205
Authors: Li Yang; Wenya Du; Zhaoyue Zheng; Li Wang; Lin Xiao; Qingzhe Yang; Qiukui Hao; Jiao Zhou; Jintao Du; Jun Li; C Alexander Valencia; Birong Dong; Hoi Yee Chow; Xianghui Fu; Biao Dong Journal: Mol Biomed Date: 2022-01-05