Hot Topics IV—Targeting Neurological Diseases by Gene Therapy Approaches

Using X-ray diffraction data, James Watson (1928-2025) made the seminal discovery of the double-helical structure of DNA together with Francis Crick (1916-2004) in 1953, a breakthrough that revealed how genetic information is stored and replicated in living organisms. For their discovery that DNA consists of two complementary, antiparallel strands held together by specific base-pairing both researchers were awarded the Nobel prize in Physiology or Medicine in 1962. The discovery laid the foundation for modern molecular biology, enabling further understanding of gene expression, heredity, and mutation.

More recently, the discovery of CRISPR/Cas9 technology by Emmanuelle Charpentier and Jennifer A. Doudna in 2012 has revolutionized the capability to incorporate gene sequences into genomes with an unprecedented level of accuracy and efficiency. In their studies, both scientists uncovered a molecular scissor, tracrRNA, involved in bacterial innate defense mechanisms. Charpentier and Doudna reprogrammed these scissors, enabling them to cleave DNA molecules at predetermined sites. For their discovery, both scientists were awarded with the Nobel Prize in Chemistry in 2020.

Gene editing and therapy have emerged as a cornerstone of modern biotechnology over the past decade. Its global utilization across bioscience domains underscores its impact and significance, and it applications have extended far into the field of clinical neurosciences. So far, gene editing and therapy has inseminated Cellular Neuropathology in the following ways:

• Treating inherited neurodegenerative diseases: Gene therapy technology holds promise for treating inherited neurodegenerative diseases in the nervous system.
• Modeling neurological disorders: Gene editing, including CRISPR/Cas9, has been used to generate cellular and animal models of various neurological disorders. This allows scientists to study disease mechanisms more accurately than before.
• Understanding neurodevelopment: By precisely manipulating genes in developing organisms, researchers have been able to uncover the roles of specific genes in brain development and modify neurodevelopmental pathologies.
• Functional genomics: Gene technology has enabled scientists to perform large-scale functional genomics studies in neural cells, identifying genes that play key roles in neural function and connectivity.
• Regenerative medicine: Gene editing technology has been investigated for promoting neuronal regeneration after CNS injuries. Targeted gene editing could potentially stimulate the growth and repair of damaged neural tissue.

In an effort to identify the most promising concepts in translational neurosciences, the Cellular Neuropathology section of Frontiers in Cellular Neurosciences recently launched a platform, the Hot Topics hub. Within this platform, this journal searches for impactful papers in Cellular Neuropathology, which carry landscape-changing potential, broaden imagination horizons and expand current diagnostic or therapeutic possibilities. Within this platform, previous Research Topics evaluated the role of subtle neuroinflammation in chronic neurodegeneration, the role of neuronal plasticity in the injured CNS and the role of gene editing in understanding neurological disease pathologies.

In commemoration of James Watson’s recent death on November 6, 2025, the Hot Topics platform of the Cellular Neuropathology section of Frontiers in Cellular Neuroscience would like to shift the focus from distinct disease processes to gene therapy, which deeply transforms several neurodegenerative diseases at this moment. As in the previous Research Topics, suitable manuscripts focusing on gene therapies should push our understanding of neurological diseases, overcome existing limitations, pave the way for therapeutic progress and deserve attention in future research developments.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: gene therapies, neurodegenerative diseases, CRISPR/Cas9 gene editing

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.