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Notch Intracellular Domain Plasmid Delivery via Poly(lactic-co-glycolic acid) Nanoparticles to Upregulate Notch Signaling

Victoria L. Messerschmidt, Aneetta E. Kuriakose, Uday Chintapula, Samantha Laboy, Thuy Thi Dang Truong, LeNaiya A. Kydd, Justyn Jaworski, Kytai T. Nguyen, View ORCID ProfileJuhyun Lee
doi: https://doi.org/10.1101/2021.04.16.440241
Victoria L. Messerschmidt
1Department of Bioengineering, University of Texas at Arlington, Arlington TX 76010 USA
2University of Texas Southwestern Medical Center, Dallas TX 75390 USA
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Aneetta E. Kuriakose
1Department of Bioengineering, University of Texas at Arlington, Arlington TX 76010 USA
2University of Texas Southwestern Medical Center, Dallas TX 75390 USA
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Uday Chintapula
1Department of Bioengineering, University of Texas at Arlington, Arlington TX 76010 USA
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Samantha Laboy
1Department of Bioengineering, University of Texas at Arlington, Arlington TX 76010 USA
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Thuy Thi Dang Truong
1Department of Bioengineering, University of Texas at Arlington, Arlington TX 76010 USA
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LeNaiya A. Kydd
1Department of Bioengineering, University of Texas at Arlington, Arlington TX 76010 USA
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Justyn Jaworski
1Department of Bioengineering, University of Texas at Arlington, Arlington TX 76010 USA
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Kytai T. Nguyen
1Department of Bioengineering, University of Texas at Arlington, Arlington TX 76010 USA
2University of Texas Southwestern Medical Center, Dallas TX 75390 USA
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  • For correspondence: juhyun.lee@uta.edu
Juhyun Lee
1Department of Bioengineering, University of Texas at Arlington, Arlington TX 76010 USA
2University of Texas Southwestern Medical Center, Dallas TX 75390 USA
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  • ORCID record for Juhyun Lee
  • For correspondence: juhyun.lee@uta.edu
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Abstract

Notch signaling is a highly conserved signaling system that is required for embryonic development and regeneration of organs. When the signal is lost, maldevelopment occurs and leads to a lethal state. Liposomes and retroviruses are most commonly used to deliver genetic material to cells. However, there are many drawbacks to these systems such as increased toxicity, nonspecific delivery, short half-life, and stability after formulation. We utilized the negatively charged and FDA approved polymer poly(lactic-co-glycolic acid) to encapsulate Notch Intracellular Domain-containing plasmid in nanoparticles. In this study, we show that primary human umbilical vein endothelial cells readily uptake the nanoparticles with and without specific antibody targets. We demonstrated that our nanoparticles also are nontoxic, stable over time, and compatible with blood. We also determined that we can successfully transfect primary human umbilical vein endothelial cells (HUVECs) with our nanoparticles in static and dynamic environments. Lastly, we elucidated that our transfection upregulates the downstream genes of Notch signaling, indicating that the payload was viable and successfully altered the genetic downstream effects.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 18, 2021.
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Notch Intracellular Domain Plasmid Delivery via Poly(lactic-co-glycolic acid) Nanoparticles to Upregulate Notch Signaling
Victoria L. Messerschmidt, Aneetta E. Kuriakose, Uday Chintapula, Samantha Laboy, Thuy Thi Dang Truong, LeNaiya A. Kydd, Justyn Jaworski, Kytai T. Nguyen, Juhyun Lee
bioRxiv 2021.04.16.440241; doi: https://doi.org/10.1101/2021.04.16.440241
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Notch Intracellular Domain Plasmid Delivery via Poly(lactic-co-glycolic acid) Nanoparticles to Upregulate Notch Signaling
Victoria L. Messerschmidt, Aneetta E. Kuriakose, Uday Chintapula, Samantha Laboy, Thuy Thi Dang Truong, LeNaiya A. Kydd, Justyn Jaworski, Kytai T. Nguyen, Juhyun Lee
bioRxiv 2021.04.16.440241; doi: https://doi.org/10.1101/2021.04.16.440241

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