Span poly-L-arginine nanoparticles are efficient non-viral vectors for PRPF31 gene delivery: An approach of gene therapy to treat retinitis pigmentosa

Pensado, Andrea; Díaz-Corrales, Francisco J.; Cerda, Berta de la; Valdés-Sánchez, Lourdes; Boz, Ana Aramburu del; Rodríguez–Martínez, Daniel; García-Delgado, Ana Belén; Seijo, Begoña; Bhattacharya, Siladitya; Sánchez, Alejandro

doi:10.1016/j.nano.2016.06.007

Cited by 19 publications

(12 citation statements)

References 34 publications

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“…All of the physical and spectroscopic data (Figures –) indicate that the hexa-arginine ligand Ac-BPA-Arg 6 -NH 2 brings about DNA condensation. This effect is involved in the use of poly-arginine in gene transfer . The kinetic assays (Figures and ) reveal that this condensation produces a substantial attenuation in the DNA reactivity with DNase I and with the hydroxyl radical.…”

Section: Discussionmentioning

confidence: 94%

Boronated Condensed DNA as a Heterochromatic Radiation Target Model

2021

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The compound 4-dihydroxyboryl-L-phenylalanine (BPA) has found use in clinical trials of boron neutron capture therapy (BNCT). Here, we have examined the interaction with DNA of an amide-blocked BPA derivative of hexa-L-arginine (Ac-BPA-Arg 6 -NH 2 ). Physical and spectroscopic assays show that this peptide binds to and condenses DNA. The resulting condensates are highly resistant to the effects of nuclease incubation (68-fold) and gamma (38-fold) irradiation. Radioprotection was modeled by Monte Carlo track structure simulations of DNA single strand breaks (SSBs) with TOPAS-nBio. The differences between experimental and simulated SSB yields for uncondensed and condensed DNAs were ca. 2 and 18%, respectively. These observations indicate that the combination of a plasmid DNA target, the BPA-containing peptide, and track structure simulation provides a powerful approach to characterize DNA damage by the high-LET radiation associated with neutron capture on boron.

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Section: Discussionmentioning

confidence: 94%

Boronated Condensed DNA as a Heterochromatic Radiation Target Model

2021

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“…However, previous data sets are limited by the use of age as the dependent variable, as PRPF31-mediated retinitis pigmentosa is characterized by a variable age of onset. 17 As it may be a candidate for gene therapy, 18 more information is needed about the natural history of PRPF31-mediated retinitis pigmentosa. In this study, we seek to clarify the disease course of PRPF31-mediated retinitis pigmentosa in a large cohort of patients.…”

Section: Introductionmentioning

confidence: 99%

Time Course of Disease Progression of PRPF31-mediated Retinitis Pigmentosa

Kiser

Webb‐Jones

Bowne

et al. 2019

American Journal of Ophthalmology

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Purpose: Variants in PRPF31, a splicing factor, are a common cause of autosomal dominant retinitis pigmentosa (RP). Deleterious variants are thought to cause disease by haploinsufficiency. In anticipation of upcoming replacement gene therapy trials, we present the phenotype and clinical progression of a large cohort of patients with PRPF31-mediated RP.Design: Cross-sectional with retrospective review Methods: A total of 26 patients with RP and 5 asymptomatic individuals, all with deleterious variants in PRPF31 (from 13 families), were selected from our database of patients followed longitudinally. Ages ranged from 9-77 years (mean 47 years old), with an average follow up time of 16 years. All patients underwent ophthalmic examination including psychophysical tests, electrophysiology, and imaging. All available records were reviewed retrospectively. Additionally, all patients were contacted, and all available patients (n=7) were examined in an additional prospective follow up visit.Results: Age of onset ranged from 6 to 71 years of age, without apparent relationship to specific variant. Two adults (ages 42 and 77) and 3 teenaged children were found to harbor a mutation with no evidence of RP. In those with RP, visual field area (spot size III) declined exponentially at a rate of 8.1% per year of disease duration (p<0.001, 95% CI 5.6-10.6), electroretinogram (ERG) cone amplitude declined exponentially at a rate of 7.3% per year of disease duration (p<0.001, 95% CI 5.4-9.1), and ellipsoid zone (EZ) area declined exponentially at a rate of 5.4% per year of disease duration (p<0.001, 95% CI 3.7-7.1).

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“…[33][34][35][36][37][38][39] Additionally, it is a semi-essential amino-acid with various roles such as in cell metabolism, wound healing, protein synthesis, and it also shows antimicrobial and antitumor activity. [40][41][42][43][44][45] In particular, owing to their favorable properties, NPs comprised of PLA have garnered considerable interest for delivery of small molecules. [46][47][48] Hence, the synthesis of ICG-PLA NPs would not only help in cellular delivery but also would improve the optical stability of ICG.…”

Section: Introductionmentioning

confidence: 99%