June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Self-Assembly ECO-Plasmid DNA Nanoparticles Facilitate Robust Gene Expression Comparable to AAV2 Vector
Author Affiliations & Notes
  • Da Sun
    Case Western Reserve University, Lyndhusrt, Ohio, United States
  • wenyu sun
    Case Western Reserve University, Lyndhusrt, Ohio, United States
  • Songqi Gao
    Case Western Reserve University, Lyndhusrt, Ohio, United States
  • Amirreza Naderi
    Case Western Reserve University, Lyndhusrt, Ohio, United States
  • Cheng Wei
    Case Western Reserve University, Lyndhusrt, Ohio, United States
  • Jonathan Lehrer
    Case Western Reserve University, Lyndhusrt, Ohio, United States
  • Xujie Liu
    Case Western Reserve University, Lyndhusrt, Ohio, United States
  • Zheng-Rong Lu
    Case Western Reserve University, Lyndhusrt, Ohio, United States
  • Footnotes
    Commercial Relationships   Da Sun, None; wenyu sun, None; Songqi Gao, None; Amirreza Naderi, None; Cheng Wei, None; Jonathan Lehrer, None; Xujie Liu, None; Zheng-Rong Lu, None
  • Footnotes
    Support  Harrington Discovery Institute and the Foundation of Fighting Blindness, and NEI R24-EY-024864 and NEI R24-EY-027283, the Canadian Institute for Advanced Research (CIFAR) and Alcon Research Institute (ARI)
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 4477. doi:
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      Da Sun, wenyu sun, Songqi Gao, Amirreza Naderi, Cheng Wei, Jonathan Lehrer, Xujie Liu, Zheng-Rong Lu; Self-Assembly ECO-Plasmid DNA Nanoparticles Facilitate Robust Gene Expression Comparable to AAV2 Vector. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4477.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Gene replacement therapy (GRT) has received increasing attention due to the success of adenoassociated virus (AAV)-based GRT for Leber’s congenital amaurosis (LCA2). However, AAVs have limited loading capacity of 4.7 kB, restricting their applications in therapies that require delivery of large genes such as Stargardt’s disease (STGD). Here, we developed a non-viral GRT based on a platform of pH-sensitive multifunctional lipid ECO with unlimited cargo capacity and compared the transfection efficiency with AAV2 using a GFP reporter gene.

Methods : Subretinal treatments were performed using retinal pigment epithelium (RPE) targeted ECO/pCMV-GFP nanoparticles and AAV2-CMV-GFP vectors with the same doses to BALB/c mice. GFP expression was examined 14 days after injection using a scanning laser ophthalmoscopy (SLO) featuring a fluorescent mode with an argon wavelengths of 488/514 nm.

Results : Subretinal delivery of both the targeted ECO/pCMV-GFP nanoparticles and AAV2-CMV-GFP vectors induced significant GFP expression comparing to untreated control (Figure 1). Both the nanoparticles and AAV2 demonstrated GFP expression across the examined retinal area. Targeted ECO-based nanoparticles demonstrated at least same level or better GFP expression than AAV2.

Conclusions : In conclusion, the targeted ECO/pCMV-GFP nanoparticles demonstrated well distributed GFP expression in BALB/c mice 14 days after treatments, comparable to the AAV2-CMV-GFP vector. The self-assembly ECO-pDNA nanoparticles have no cargo size limitation and can be a promising non-viral GRT for a broad range of monogenic retinal disorders.

This is a 2020 ARVO Annual Meeting abstract.

 

Figure 1. Comparison of in vivo gene expression efficiency of ECO and AAV2 demonstrated by SLO fluorescent imaging of the treated retina 14 days after subretinal injection. White dots indicated GFP expression in the retinal tissue.

Figure 1. Comparison of in vivo gene expression efficiency of ECO and AAV2 demonstrated by SLO fluorescent imaging of the treated retina 14 days after subretinal injection. White dots indicated GFP expression in the retinal tissue.

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