@article{e725e88bf0cb4fb5b633372f0ce2a70f,
title = "An in vivo Cell-Based Delivery Platform for Zinc Finger Artificial Transcription Factors in Pre-clinical Animal Models",
abstract = "Zinc finger (ZF), transcription activator-like effectors (TALE), and CRISPR/Cas9 therapies to regulate gene expression are becoming viable strategies to treat genetic disorders, although effective in vivo delivery systems for these proteins remain a major translational hurdle. We describe the use of a mesenchymal stem/stromal cell (MSC)-based delivery system for the secretion of a ZF protein (ZF-MSC) in transgenic mouse models and young rhesus monkeys. Secreted ZF protein from mouse ZF-MSC was detectable within the hippocampus 1 week following intracranial or cisterna magna (CM) injection. Secreted ZF activated the imprinted paternal Ube3a in a transgenic reporter mouse and ameliorated motor deficits in a Ube3a deletion Angelman Syndrome (AS) mouse. Intrathecally administered autologous rhesus MSCs were well-tolerated for 3 weeks following administration and secreted ZF protein was detectable within the cerebrospinal fluid (CSF), midbrain, and spinal cord. This approach is less invasive when compared to direct intracranial injection which requires a surgical procedure.",
keywords = "Angelman Syndrome (AS), artificial transcription factor (ATF), cell-based delivery, mesenchymal stem/stromal cell, zinc finger",
author = "Peter Deng and Halmai, {Julian A.N.M.} and Ulrika Beitnere and David Cameron and Martinez, {Michele L.} and Lee, {Charles C.} and Waldo, {Jennifer J.} and Krista Thongphanh and Anna Adhikari and Nycole Copping and Petkova, {Stela P.} and Lee, {Ruth D.} and Samantha Lock and Miranda Palomares and Henriette O{\textquoteright}Geen and Jasmine Carter and Gonzalez, {Casiana E.} and Buchanan, {Fiona K.B.} and Anderson, {Johnathan D.} and Fierro, {Fernando A.} and Nolta, {Jan A.} and Tarantal, {Alice F.} and Silverman, {Jill L.} and Segal, {David J.} and Fink, {Kyle D.}",
note = "Funding Information: The studies described was supported by a CIRM Discovery Grant DISC2-09032, Diversity Supplement 3R24OD021606-02ZF, NIGMS Pharmacology T32 GM099608, NIH NCATS UL1 TR001860 and linked award TL1 TR001861 (mice); and a California National Primate Research Center pilot project award (rhesus monkeys; NIH P51-OD011107). The Dickenson{\textquoteright}s Catalyst Fund, A Stewart{\textquoteright}s and Dake Family Gift, HELP4HD International, WeHaveAFace.org, and philanthropic donors from the Huntington{\textquoteright}s Disease community, including the Roberson family and Team KJ, also contributed to these studies. BLI was performed in rhesus monkeys with instrumentation obtained through a NIH S10 award to AT (S10-OD018102). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Funding Information: The studies described was supported by a CIRM Discovery Grant DISC2-09032, Diversity Supplement 3R24OD021606-02ZF, NIGMS Pharmacology T32 GM099608, NIH NCATS UL1 TR001860 and linked award TL1 TR001861 (mice); and a California National Primate Research Center pilot project award (rhesus monkeys; NIH P51-OD011107). The Dickenson?s Catalyst Fund, A Stewart?s and Dake Family Gift, HELP4HD International, WeHaveAFace.org, and philanthropic donors from the Huntington?s Disease community, including the Roberson family and Team KJ, also contributed to these studies. BLI was performed in rhesus monkeys with instrumentation obtained through a NIH S10 award to AT (S10-OD018102). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: Copyright {\textcopyright} 2022 Deng, Halmai, Beitnere, Cameron, Martinez, Lee, Waldo, Thongphanh, Adhikari, Copping, Petkova, Lee, Lock, Palomares, O{\textquoteright}Geen, Carter, Gonzalez, Buchanan, Anderson, Fierro, Nolta, Tarantal, Silverman, Segal and Fink.",
year = "2022",
month = jan,
day = "27",
doi = "10.3389/fnmol.2021.789913",
language = "English (US)",
volume = "14",
journal = "Frontiers in Molecular Neuroscience",
issn = "1662-5099",
publisher = "Frontiers Research Foundation",
}