Woodard Lauren E, Welch Richard C, Menshikh Anna, Luo Wentian, Williams Felisha M, Peek Jennifer L, Sha Feng, Veach Ruth Ann, Kaja Aparna, Beckerman Thomas M, Ikizler Talat Alp, Wilson Matthew H
Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Department of Veterans Affairs, Tennessee Valley Health Services, Nashville, TN 37212, USA.
Mol Ther Nucleic Acids. 2025 Jul 21;36(3):102639. doi: 10.1016/j.omtn.2025.102639. eCollection 2025 Sep 9.
We used kidney-targeted, non-viral, transposon-mediated gene delivery to express the mouse transgene in one kidney of cystinuria type A ( ) mice. We found a 44% reduction in urinary cystine concentration at 154 days post-gene transfer, although there was no significant effect on cystine stone formation. Our results indicate that it is possible to achieve kidney-targeted gene transfer, resulting in reduction of cystine concentration in the urine of a cystinuria type A animal model. This proof of concept lays the foundation for future studies directed at gene therapy for cystinuria and other kidney diseases.
我们采用肾脏靶向、非病毒、转座子介导的基因递送方法，在A型胱氨酸尿症（ ）小鼠的一侧肾脏中表达小鼠转基因。我们发现，基因转移后154天时，尿胱氨酸浓度降低了44%，尽管对胱氨酸结石形成没有显著影响。我们的结果表明，实现肾脏靶向基因转移并降低A型胱氨酸尿症动物模型尿液中的胱氨酸浓度是可能的。这一概念验证为未来针对胱氨酸尿症和其他肾脏疾病的基因治疗研究奠定了基础。
