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Cited by 158Virus-based gene therapy researchRNA Interference and Gene DeliveryBarrier Structure and Function Studies

Gene Therapy Tools for Brain Diseases

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Ingusci, Selene, Verlengia, Gianluca, Soukupova, Marie, Zucchini, Silvia, Simonato, Michele·2019·Frontiers in Pharmacology
DOI 10.3389/fphar.2019.00724PMC PMC6613496
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Abstract

Neurological disorders affecting the central nervous system (CNS) are still incompletely understood. Many of these disorders lack a cure and are seeking more specific and effective treatments. In fact, in spite of advancements in knowledge of the CNS function, the treatment of neurological disorders with modern medical and surgical approaches remains difficult for many reasons, such as the complexity of the CNS, the limited regenerative capacity of the tissue, and the difficulty in conveying conventional drugs to the organ due to the blood-brain barrier. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. Gene therapy can result in a stable or inducible expression of transgene(s), and can allow a nearly specific expression in target cells. In this review, we will discuss the most commonly used tools for the delivery of genetic material in the CNS, including viral and non-viral vectors; their main applications; their advantages and disadvantages. We will discuss mechanisms of genetic regulation through cell-specific and inducible promoters, which allow to express gene products only in specific cells and to control their transcriptional activation. In addition, we will describe the applications to CNS diseases of post-transcriptional regulation systems (RNA interference); of systems allowing spatial or temporal control of expression [optogenetics and Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)]; and of gene editing technologies (CRISPR/Cas9, Zinc finger proteins). Particular attention will be reserved to viral vectors derived from herpes simplex type 1, a potential tool for the delivery and expression of multiple transgene cassettes simultaneously.

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  • Most genetic brain diseases lack reasonably effective therapies due to the complexity of the CNS, the limited regenerative capacity of the tissue, and the difficulty of therapeutics crossing the blood-brain barrier.

    “Most genetic brain diseases lack reasonably effective therapies due to the complexity of the CNS, the limited regenerative capacity of the tissue, and the difficulty of therapeutics crossing the blood-brain barrier (37).”

    From Ionizable Lipid Nanoparticles for Therapeutic Base Editing of Congenital Brain Disease (2023) · cites this paper as [37]

    The Introduction says that the majority of neurological disorders affecting the CNS lack a cure or reasonably effective treatment, and names CNS complexity, limited regeneration, and difficulty crossing the blood–brain barrier as reasons. It does not establish that this is true specifically of most genetic brain diseases. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

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Authors
Ingusci, S., Verlengia, G., Soukupova, M., Zucchini, S., & Simonato, M.
Affiliations
  • University of Ferrara (IT)
  • Vita-Salute San Raffaele University (IT)
Corresponding author
Ingusci, Selene
ORCID
Venue
Frontiers in Pharmacology
Publisher
Frontiers Media SA
Published
2019-07-01
Volume
10
Pages
724-724
ISSN
1663-9812 (ISSN-L)
DOI
10.3389/fphar.2019.00724
PMC
PMC6613496
OpenAlex
W2955720713
Cited by
158
References
22
Citations by year
2026: 3 · 2025: 23 · 2024: 21 · 2023: 23 · 2022: 23 · 2021: 42 · 2020: 22 · 2019: 1
FWCI
2.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Pharmacology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
European Commission
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords
gene therapy, central nervous system disorders, neurological disorders, gene delivery vectors, viral vectors, non-viral vectors, herpes simplex virus type 1 vectors, inducible promoters, cell-specific promoters, RNA interference, optogenetics, DREADD, CRISPR/Cas9, zinc finger proteins, blood-brain barrier, transgene expression

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