The DOI matches its Crossref record; 259 of the 259 references it cites were found in a registry or an index.
Destination Brain: the Past, Present, and Future of Therapeutic Gene Delivery
Open accessAbstract
Neurological diseases and disorders (NDDs) present a significant societal burden and currently available drug- and biological-based therapeutic strategies have proven inadequate to alleviate it. Gene therapy is a suitable alternative to treat NDDs compared to conventional systems since it can be tailored to specifically alter select gene expression, reverse disease phenotype and restore normal function. The scope of gene therapy has broadened over the years with the advent of RNA interference and genome editing technologies. Consequently, encouraging results from central nervous system (CNS)-targeted gene delivery studies have led to their transition from preclinical to clinical trials. As we shift to an exciting gene therapy era, a retrospective of available literature on CNS-associated gene delivery is in order. This review is timely in this regard, since it analyzes key challenges and major findings from the last two decades and evaluates future prospects of brain gene delivery. We emphasize major areas consisting of physiological and pharmacological challenges in gene therapy, function-based selection of a ideal cellular target(s), available therapy modalities, and diversity of viral vectors and nanoparticles as vehicle systems. Further, we present plausible answers to key questions such as strategies to circumvent low blood-brain barrier permeability and most suitable CNS cell types for targeting. We compare and contrast pros and cons of the tested viral vectors in the context of delivery systems used in past and current clinical trials. Gene vector design challenges are also evaluated in the context of cell-specific promoters. Key challenges and findings reported for recent gene therapy clinical trials, assessing viral vectors and nanoparticles are discussed from the perspective of bench to bedside gene therapy translation. We conclude this review by tying together gene delivery challenges, available vehicle systems and comprehensive analyses of neuropathogenesis to outline future prospects of CNS-targeted gene therapies.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“AAV vector administration to the CNS has an excellent safety and efficacy profile.”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [53]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Vos, T., Abajobir, A. A., Abate, K. H., Abbafati, C., Abbas, K. M., Abd-Allah, F., Abdulkader, R. S., Abdulle, A. M., Abebo, T. A., Abera, S. F., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)32154-2 · Cited by 13,220
Polazzi, E., Mengoni, I., Caprini, M., Peña‐Altamira, E., Kurtys, E., & Monti, B. (2012) · Neurosignals · doi:10.1159/000337115 · Cited by 9,023
Vos, T., Barber, R. M., Bell, B., Bertozzi-Villa, A., Biryukov, S., Bolliger, I., Charlson, F., Davis, A., Degenhardt, L., Dicker, D., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(15)60692-4 · Cited by 6,414
Astrocyte-endothelial interactions at the blood-brain barrier
Abbott, N. J., Rönnbäck, L., & Hansson, E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1824 · Cited by 5,595
In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector
Naldini, L., Blömer, U., Gallay, P., Ory, D., Mulligan, R., Gage, F. H., Verma, I. M., & Trono, D. (1996) · Science · doi:10.1126/science.272.5259.263 · Cited by 4,903
Microglia-mediated neurotoxicity: uncovering the molecular mechanisms
Block, M. L., Zecca, L., & Hong, J.-S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2038 · Cited by 4,110
ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering
Gaj, T., Gersbach, C. A., & Barbas, C. F. (2013) · Trends in Biotechnology · doi:10.1016/j.tibtech.2013.04.004 · Cited by 3,820
Aggregation of Huntingtin in Neuronal Intranuclear Inclusions and Dystrophic Neurites in Brain
DiFiglia, M., Sapp, E., Chase, K. O., Davies, S. W., Bates, G. P., Vonsattel, J. P., & Aronin, N. (1997) · Science · doi:10.1126/science.277.5334.1990 · Cited by 2,439
Bellini, M., Charalampidis, S., Herbert, P., Bonatsos, V., Crane, J., Muthusamy, A., Dor, F., & Papalois, V. E. (2022) · BioMed Research International · doi:10.1155/2738 · Cited by 2,431
Neuroinflammation in Parkinson’s disease: A target for neuroprotection?
Hirsch, E. C., & Hunot, S. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70062-6 · Cited by 1,984
Cited by
Sorted by citations
Polyethylenimine (PEI) in gene therapy: Current status and clinical applications
Casper, J., Schenk, S., Parhizkar, E., Detampel, P., Dehshahri, A., & Huwyler, J. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.09.001 · Cited by 360
New Advances in General Biomedical Applications of PAMAM Dendrimers
de Araújo, R. V., Santos, S. D. S., Ferreira, E. I., & Giarolla, J. (2018) · Molecules · doi:10.3390/molecules23112849 · Cited by 279
Potential of Chitosan and Its Derivatives for Biomedical Applications in the Central Nervous System
Ojeda-Hernández, D. D., Canales-Aguirre, A. A., Matías‐Guiu, J., Gómez‐Pinedo, U., & Mateos‐Díaz, J. C. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00389 · Cited by 175
AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease
Rosenberg, J. B., Kaplitt, M. G., De, B. P., Chen, A., Flagiello, T., Salami, C., Pey, E., Zhao, L., Ricart Arbona, R. J., Monette, S., et al. (2018) · Human Gene Therapy Clinical Development · doi:10.1089/humc.2017.231 · Cited by 176
Helmschrodt, C., Höbel, S., Schöniger, S., Bauer, A., Bonicelli, J., Gringmuth, M., Fietz, S. A., Aigner, A. M., Richter, A., & Richter, F. (2017) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2017.08.013 · Cited by 154
Metadata
- Authors
- Joshi, C. R., Labhasetwar, V., & Ghorpade, A.
- Affiliations
- University of North Texas Health Science Center (US)
- Cleveland Clinic (US)
- Corresponding author
- Ghorpade, Anuja
- Venue
- Journal of Neuroimmune Pharmacology
- Published
- 2017-02-03
- Volume
- 12
- Issue
- 1
- Pages
- 51-83
- ISSN
- 1557-1890 (ISSN-L)
- 1557-1904
- PMC
- PMC5393046
- OpenAlex
- W2585557706
- Cited by
- 55
- References
- 259
- Citations by year
- 2025: 4 · 2024: 8 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 10 · 2019: 5 · 2018: 10 · 2017: 7
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Journal of Neuroimmune Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS048837, NS070896)
- 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, gene delivery to the brain, central nervous system, neurological disorders, blood-brain barrier, viral vectors, nanoparticles, RNA interference, genome editing, cell-specific promoters, clinical trials, translational medicine, neuropathogenesis
- MeSH terms
- Animals, Blood-Brain Barrier, Brain, Forecasting, Humans, Genetic Therapy, Gene Transfer Techniques, Neurodegenerative Diseases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
