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Special Issue "Transcriptional Therapy and Nucleic Acid-Based Therapeutics: From Molecular Targets to Preclinical Studies"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 April 2021.

Special Issue Editor

Prof. Vincenza Barresi
Website
Guest Editor
Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, 95123 Catania, Italy
Interests: Genomics; Transcriptomics; Colorectal Cancer; Molecular Biomarkers

Special Issue Information

Colleagues,

In the last few decades, the exponential growth of genomic information has become crucial to develop new treatments based on molecular tools able to modify transcriptionally or post-transcriptionally the expression of coding and non-coding RNA. To date, antisense oligonucleotides (ASOs), apatmers and RNA Interference (RNAi), and CRISPR/Cas9 systems are the most common tools used for transcriptional therapy, and some of these tools have been approved by regulatory authorities for the therapy of diseases such as age-related macular degeneration (AMD), Duchenne muscular dystrophy (DMD), and spinal muscular atrophy (SMA). These approaches are exciting and advantageous for both monogenic and polygenic diseases. In the latter case, autoimmune and inflammatory diseases, neurological diseases, cancer, metabolic syndrome, and obesity represent the areas where transcriptional therapy and nucleic acid-based therapeutics are continuing to expand.

This Special Issue will gather a collection of papers reporting on investigations focused on concepts, interpretations, and experiments concerning nucleic acid-based therapeutics, ranging from the identification of molecular targets to their application in preclinical studies.

Prof. Vincenza Barresi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Antisense oligonucleotides
  • siRNA
  • CRISPR/Cas9
  • miRNA
  • nucleic acid-based therapeutics
  • transcriptional therapy
  • cancer therapy

Published Papers (2 papers)

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Research

Open AccessArticle
Dual Fluorescence Splicing Reporter Minigene Identifies an Antisense Oligonucleotide to Skip Exon v8 of the CD44 Gene
Int. J. Mol. Sci. 2020, 21(23), 9136; https://doi.org/10.3390/ijms21239136 - 30 Nov 2020
Abstract
Splicing reporter minigenes are used in cell-based in vitro splicing studies. Exon skippable antisense oligonucleotide (ASO) has been identified using minigene splicing assays, but these assays include a time- and cost-consuming step of reverse transcription PCR amplification. To make in vitro splicing assay [...] Read more.
Splicing reporter minigenes are used in cell-based in vitro splicing studies. Exon skippable antisense oligonucleotide (ASO) has been identified using minigene splicing assays, but these assays include a time- and cost-consuming step of reverse transcription PCR amplification. To make in vitro splicing assay easier, a ready-made minigene (FMv2) amenable to quantitative splicing analysis by fluorescence microscopy was constructed. FMv2 was designed to encode two fluorescence proteins namely, mCherry, a transfection marker and split eGFP, a marker of splicing reaction. The split eGFP was intervened by an artificial intron containing a multicloning site sequence. Expectedly, FMv2 transfected HeLa cells produced not only red mCherry but also green eGFP signals. Transfection of FMv2CD44v8, a modified clone of FMv2 carrying an insertion of CD44 exon v8 in the multicloning site, that was applied to screen exon v8 skippable ASO, produced only red signals. Among seven different ASOs tested against exon v8, ASO#14 produced the highest index of green signal positive cells. Hence, ASO#14 was the most efficient exon v8 skippable ASO. Notably, the well containing ASO#14 was clearly identified among the 96 wells containing randomly added ASOs, enabling high throughput screening. A ready-made FMv2 is expected to contribute to identify exon skippable ASOs. Full article
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Open AccessArticle
Translational Read-Through Therapy of RPGR Nonsense Mutations
Int. J. Mol. Sci. 2020, 21(22), 8418; https://doi.org/10.3390/ijms21228418 - 10 Nov 2020
Abstract
X-chromosomal retinitis pigmentosa (RP) frequently is caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. We evaluated the potential of PTC124 (Ataluren, TranslamaTM) treatment to promote ribosomal read-through of premature termination codons (PTC) in RPGR. Expression [...] Read more.
X-chromosomal retinitis pigmentosa (RP) frequently is caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. We evaluated the potential of PTC124 (Ataluren, TranslamaTM) treatment to promote ribosomal read-through of premature termination codons (PTC) in RPGR. Expression constructs in HEK293T cells showed that the efficacy of read-through reagents is higher for UGA than UAA PTCs. We identified the novel hemizygous nonsense mutation c.1154T > A, p.Leu385* (NM_000328.3) causing a UAA PTC in RPGR and generated patient-derived fibroblasts. Immunocytochemistry of serum-starved control fibroblasts showed the RPGR protein in a dot-like expression pattern along the primary cilium. In contrast, RPGR was no longer detectable at the primary cilium in patient-derived cells. Applying PTC124 restored RPGR at the cilium in approximately 8% of patient-derived cells. RT-PCR and Western blot assays verified the pathogenic mechanisms underlying the nonsense variant. Immunofluorescence stainings confirmed the successful PTC124 treatment. Our results showed for the first time that PTC124 induces read-through of PTCs in RPGR and restores the localization of the RPGR protein at the primary cilium in patient-derived cells. These results may provide a promising new treatment option for patients suffering from nonsense mutations in RPGR or other genetic diseases. Full article
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