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Peer-reviewedCC BYGenes

Kidney-Targeted Gene Transfer: Therapeutic Advances in Native Kidney Disease and Emerging Ex Vivo Allograft Engineering.

  • Yongfa Lei1,2,3,4,5
  • Ruying Zheng1,2,3,4,5
  • Daqiang Zhao1,2,3,4,5
5 affiliations
  1. 1Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  2. 2Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan 430030, China.
  3. 3National Health Commission Key Laboratory of Organ Transplantation, Wuhan 430030, China.
  4. 4Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, China.
  5. 5Hubei Provincial Clinical Research Center for Organ Transplantation, Wuhan 430030, China.
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Abstract

Kidney-targeted gene transfer is progressing toward two distinct clinical applications: correcting molecular defects or modifying disease pathways in native kidneys and modifying donor kidneys before allotransplantation to reduce ischemia-reperfusion injury or rejection. These applications share a delivery challenge but differ in their target cells, therapeutic mechanisms, required duration and acceptable systemic exposure. Advances in renal delivery have produced disease benefit in selected animal models, while ex vivo perfusion offers a controlled opportunity to expose and assess a graft before implantation. Neither renal vector detection nor reporter expression alone establishes therapeutic efficacy. This review evaluates the evidence through four linked layers: vector distribution, cell-resolved delivery or expression, therapeutic target engagement and functional benefit. It compares candidate strategies according to indication and duration, distinguishes capsid tropism from promoter-mediated expression bias and separates demonstrated outcomes from mechanistic proposals. For donor-kidney engineering, limited treatment time, uneven intrarenal delivery, perfusion injury and delayed vector release after reperfusion remain central constraints. Translation will require indication-specific dose-response studies, human-relevant delivery assessment and surveillance extending beyond early benefit or transient immune silencing. Progress therefore depends on a coherent therapeutic configuration, rather than a universal kidney vector.

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Cite

BibTeXRIS
BibTeX
@article{lei2026kidneytargeted,
  title = {{Kidney-Targeted Gene Transfer: Therapeutic Advances in Native Kidney Disease and Emerging Ex Vivo Allograft Engineering.}},
  author = {Yongfa Lei and Ruying Zheng and Daqiang Zhao},
  journal = {Genes},
  year = {2026},
  month = oct,
  doi = {10.3390/genes17101270},
  url = {https://europepmc.org/article/MED/42938385},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Kidney-Targeted Gene Transfer: Therapeutic Advances in Native Kidney Disease and Emerging Ex Vivo Allograft Engineering.
AU  - Yongfa Lei
AU  - Ruying Zheng
AU  - Daqiang Zhao
PY  - 2026
DA  - 2026/10/13
JO  - Genes
DO  - 10.3390/genes17101270
UR  - https://europepmc.org/article/MED/42938385
AB  - Kidney-targeted gene transfer is progressing toward two distinct clinical applications: correcting molecular defects or modifying disease pathways in native kidneys and modifying donor kidneys before allotransplantation to reduce ischemia-reperfusion injury or rejection. These applications share a delivery challenge but differ in their target cells, therapeutic mechanisms, required duration and acceptable systemic exposure. Advances in renal delivery have produced disease benefit in selected animal models, while ex vivo perfusion offers a controlled opportunity to expose and assess a graft before implantation. Neither renal vector detection nor reporter expression alone establishes therapeutic efficacy. This review evaluates the evidence through four linked layers: vector distribution, cell-resolved delivery or expression, therapeutic target engagement and functional benefit. It compares candidate strategies according to indication and duration, distinguishes capsid tropism from promoter-mediated expression bias and separates demonstrated outcomes from mechanistic proposals. For donor-kidney engineering, limited treatment time, uneven intrarenal delivery, perfusion injury and delayed vector release after reperfusion remain central constraints. Translation will require indication-specific dose-response studies, human-relevant delivery assessment and surveillance extending beyond early benefit or transient immune silencing. Progress therefore depends on a coherent therapeutic configuration, rather than a universal kidney vector.
SN  - 2073-4425
ER  -