Over the past twenty years, viral vectors, such as adeno-associated viruses (AAVs) and lentiviruses, have emerged as a paradigm shifting tool for both research and clinical applications related to the central nervous system (CNS). Recently, the explosion of new serotypes and promoters have allowed for unprecedented new capabilities, including specificity of transgene expression to targeted tissues and cell-types. For basic research, this has led to revolutionary new methods for neuroanatomical tracing, circuit manipulations such as optogenetics and DREADDs, calcium imaging technologies, and other novel approaches. In the clinic, the capabilities of viral vectors, such as AAVs, have allowed for remarkable new gene therapy potentials, owing to their targeting capabilities and their relative safety, leading to a renaissance in the treatment of diseases of the CNS.
Viral vector-based gene therapy (including adeno-associated viruses (AAVs), lentivirus, and others) has emerged as a critical new tool to treat a variety of CNS diseases that suffer from a critical unmet need, owing to a paucity of effective interventions from more traditional approaches, such as small-molecule drugs. The earliest applications of viral vectors to treat CNS disease have focused on monogenic disorders, where the goal was clear: replace the affected gene. These approaches have proven efficacious as evidenced by recently approved AAV-based gene therapy products, which essentially cure diseases with a single application. As viral vector-based gene therapy has come of age, the diseases under consideration in current clinical trials and pre-clinical development are multi-factorial disorders, where the strategy required is necessarily more complex.
In this Frontiers in Neurology Research Topic, our goal is to focus on recently developed and upcoming tools for viral vector-based gene therapy in the CNS, including novel capsids, new promoters that allow for precise targeting of cellular subtypes, and innovative transgene approaches to treating neurological conditions ranging from epilepsies to neurodegenerative disorders and beyond. We also look to foster discussions of creative uses of technology to apply and interact with viral vector-based gene therapies, aiding in both treatment and diagnosis of disease. Finally, we set out to discuss ethical concerns arising around this technology, as it will undoubtedly remodel the clinical landscape.
We welcome Original Research and Methods articles focused on new advances in capsid and promoter discovery for viral vector applications in the CNS, including new approaches being taken to identify new capsids (directed evolution, high-throughput capsid libraries, etc.) and new promoter/enhancers for target selectivity. We welcome manuscripts on advances in viral vector-based gene therapies for treating diseases CNS including:
• Epilepsies, both genetic and non-genetic phenotypes;
• Developmental and age-related neurodegenerative disorders;
• Other genetics disorder of the CNS.
Review and Mini-Review articles are also welcome pertaining to the use of viral vectors to treat CNS diseases. We also welcome Perspective and Opinion articles discussing:
• Implications of viral vector-based therapies in altering the mind;
• Clinical safety and ethical concerns regarding vector-based gene therapies, especially as a prophylactic treatment.
Finally, we welcome Hypothesis and Theory articles which outline new strategies for applications of viral vector-based gene therapy, including the potential of coupling gene therapy with other technologies to advance treatment and diagnosis of CNS diseases.
We would like to acknowledge that Dr. Danielle Sliter, National Institute of Neurological Disorders and Stroke, has acted as a coordinator and has contributed to the preparation of the proposal for this Research Topic.
Topic Editors Jared Brent Smith and Andrew Mercer are employed by REGENXBIO. All other Topic Editors declare no competing interests with regards to the Research Topic subject.