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Recombinant Adeno-associated Viral Vectors Serotypes 6 and 9 are Able to Transduce Human Tracheal Epithelial Cells but Not Human Induced Pluripotent Stem Cells

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Abstract

Recombinant adeno-associated viruses (rAAVs) may be useful for the development of gene therapy for hereditary diseases. Patient-specific human induced pluripotent stem cells (hiPSCs) can be differentiated into a variety of cells which are difficult or impossible to obtain by biopsy. To date, few research on the efficiency of rAAV transduction of hiPSCs has been published, but the obtained data are very contradictory and do not answer the actual question: how effective are rAAVs for the delivery of transgenes into hiPSCs. In this work, we used rAAV serotypes 5, 6, and 9 carrying the GFP transgene. The transduction efficiency of rAAV2/9-GFP and rAAV2/6-GFP for the immortalized tracheal epithelial cell line derived from a patient with cystic fibrosis (CFTE29o-) was relatively high. At the same time, the efficiency of transduction of iPSCs from a healthy donor and a cystic fibrosis (CF) donor was extremely low. Thus, our results show that the efficiency of hiPSC transduction by rAAV serotypes 5, 6, and 9 is not suitable for the delivery of transgenes.

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Acknowledgements

We thank Dr. S.P. Chumakov from the Institute of Bioorganic Chemistry (Moscow, Russia) for providing the pAAV-CMV-GFP plasmid and Dr. S.V. Kostyuk, the Head of the Laboratory of Molecular Biology of the Research Centre for Medical Genetics (Moscow, Russia), for providing a CHO cell line.

Funding

This work was supported by the Ministry of Science and Higher Education of the Russian Federation.

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Authors and Affiliations

  1. Research Centre for Medical Genetics, Moskvorechye 1, Moscow, 115478, Russia

    L. Belova, A. Demchenko, K. Kochergin-Nikitsky, E. Kondrateva, Ya. Slesarenko, D. Salikhova, A. Lavrov, A. Efremova, T. Bukharova, D. Goldshtein & S. Smirnikhina

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All authors have made substantial contributions to the conception of the work, wrote the manuscript and critically revised it for important intellectual content, approved the version to be published, agreed to be accountable for all aspects of the work, ensuring that issues related to the accuracy or integrity of any part of the work are properly researched.

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Correspondence to L. Belova.

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The study was approved by the Ethics Committee of the Research Centre for Medical Genetics (Moscow, Russia) and was conducted in accordance with the provisions of the 1975 Declaration of Helsinki.

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Belova, L., Demchenko, A., Kochergin-Nikitsky, K. et al. Recombinant Adeno-associated Viral Vectors Serotypes 6 and 9 are Able to Transduce Human Tracheal Epithelial Cells but Not Human Induced Pluripotent Stem Cells. Mol Biotechnol 65, 1539–1546 (2023). https://doi.org/10.1007/s12033-023-00668-4

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