Partial correction of cystinuria type A in mice via kidney-targeted transposon delivery
We used kidney-targeted, non-viral, transposon-mediated gene delivery to express the mouse Slc3a1 transgene in one kidney of cystinuria type A (Slc3a1−/−) mice. We found a 44% reduction in urinary cystine concentration at 154 days post-gene transfer, although there was no significant effect on cysti...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253125001933 |
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| author | Lauren E. Woodard Richard C. Welch Anna Menshikh Wentian Luo Felisha M. Williams Jennifer L. Peek Feng Sha Ruth Ann Veach Aparna Kaja Thomas M. Beckerman Talat Alp Ikizler Matthew H. Wilson |
| author_facet | Lauren E. Woodard Richard C. Welch Anna Menshikh Wentian Luo Felisha M. Williams Jennifer L. Peek Feng Sha Ruth Ann Veach Aparna Kaja Thomas M. Beckerman Talat Alp Ikizler Matthew H. Wilson |
| author_sort | Lauren E. Woodard |
| collection | DOAJ |
| description | We used kidney-targeted, non-viral, transposon-mediated gene delivery to express the mouse Slc3a1 transgene in one kidney of cystinuria type A (Slc3a1−/−) 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. |
| format | Article |
| id | doaj-art-6af14bc94e1f4feeb8a8d9700b6526c1 |
| institution | Matheson Library |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-6af14bc94e1f4feeb8a8d9700b6526c12025-08-02T04:47:06ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-09-01363102639Partial correction of cystinuria type A in mice via kidney-targeted transposon deliveryLauren E. Woodard0Richard C. Welch1Anna Menshikh2Wentian Luo3Felisha M. Williams4Jennifer L. Peek5Feng Sha6Ruth Ann Veach7Aparna Kaja8Thomas M. Beckerman9Talat Alp Ikizler10Matthew H. Wilson11Department 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; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, USADepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USAMedical Scientist Training Program, Vanderbilt University, Nashville, TN 37232, USA; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USADepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment 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, USADepartment 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; Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA; Corresponding author: Matthew H. Wilson, MD, PhD, Professor, Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, 1161 21st Ave South, S-3223 MCN, Nashville, TN 37232, USA.We used kidney-targeted, non-viral, transposon-mediated gene delivery to express the mouse Slc3a1 transgene in one kidney of cystinuria type A (Slc3a1−/−) 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.http://www.sciencedirect.com/science/article/pii/S2162253125001933MT: Oligonucleotides: Therapies and Applicationskidneygene therapycystinuriarBATSlc3a1 |
| spellingShingle | Lauren E. Woodard Richard C. Welch Anna Menshikh Wentian Luo Felisha M. Williams Jennifer L. Peek Feng Sha Ruth Ann Veach Aparna Kaja Thomas M. Beckerman Talat Alp Ikizler Matthew H. Wilson Partial correction of cystinuria type A in mice via kidney-targeted transposon delivery Molecular Therapy: Nucleic Acids MT: Oligonucleotides: Therapies and Applications kidney gene therapy cystinuria rBAT Slc3a1 |
| title | Partial correction of cystinuria type A in mice via kidney-targeted transposon delivery |
| title_full | Partial correction of cystinuria type A in mice via kidney-targeted transposon delivery |
| title_fullStr | Partial correction of cystinuria type A in mice via kidney-targeted transposon delivery |
| title_full_unstemmed | Partial correction of cystinuria type A in mice via kidney-targeted transposon delivery |
| title_short | Partial correction of cystinuria type A in mice via kidney-targeted transposon delivery |
| title_sort | partial correction of cystinuria type a in mice via kidney targeted transposon delivery |
| topic | MT: Oligonucleotides: Therapies and Applications kidney gene therapy cystinuria rBAT Slc3a1 |
| url | http://www.sciencedirect.com/science/article/pii/S2162253125001933 |
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