ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017
CRISPR Epigenome Editing of AKAP150 in DRG Neurons Abolishes Degenerative IVD-Induced Neuronal Activation.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 45 citations in OpenAlex.
- CRISPR Epigenome Editing of IL1R1 Expression of Neurons that Innervate the Temporomandibular Joint or Knee Causes Reduced Sensitization to Osteoarthritic Environment.Annals of biomedical engineering · 2026Article
- Stem cell therapy for degenerative disc disease: A systematic review of preclinical evidence, clinical translation, and future directions.North American Spine Society journal · 2026Review
- Understanding the Microenvironment of Intervertebral Disc Degeneration: A Comprehensive Review of Pathophysiological Insights and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Targeted CRISPR regulation of ZNF865 enhances stem cell cartilage deposition, tissue maturation rates, and mechanical properties in engineered intervertebral discs.Acta biomaterialia · 2025Article
- Harnessing CRISPR potential for intervertebral disc regeneration strategies.Frontiers in bioengineering and biotechnology · 2025Review
- pH: A major player in degenerative intervertebral disks.JOR spine · 2024Review
- Therapeutic CRISPR epigenome editing of inflammatory receptors in the intervertebral disc.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Role of oxidative stress in mitochondrial dysfunction and their implications in intervertebral disc degeneration: Mechanisms and therapeutic strategies.Journal of orthopaedic translation · 2024Review
- Review
- Use of CRISPRoff and synthetic Notch to modulate and relay endogenous gene expression programs in engineered cells.Frontiers in bioengineering and biotechnology · 2024Article
- Multifaceted Roles of ALK Family Receptors and Augmentor Ligands in Health and Disease: A Comprehensive Review.Biomolecules · 2023Review
- Multiplex gene editing to promote cell survival using low-pH clustered regularly interspaced short palindromic repeats activation (CRISPRa) gene perturbation.Cytotherapy · 2023Article
- Article
- Imaging Evaluation of Intervertebral Disc Degeneration and Painful Discs-Advances and Challenges in Quantitative MRI.Diagnostics (Basel, Switzerland) · 2022Review
- Disruptors of AKAP-Dependent Protein-Protein Interactions.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Emerging strategies for the genetic dissection of gene functions, cell types, and neural circuits in the mammalian brain.Molecular psychiatry · 2022Review
- Degenerative IVD conditioned media and acidic pH sensitize sensory neurons to cyclic tensile strain.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2021Article
- Cell-based strategies for IVD repair: clinical progress and translational obstacles.Nature reviews. Rheumatology · 2021Review
- Genetic Therapy for Intervertebral Disc Degeneration.International journal of molecular sciences · 2021Review
- AKAP Signaling Islands: Venues for Precision Pharmacology.Trends in pharmacological sciences · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Back pain is a major contributor to disability and has significant socioeconomic impacts worldwide. The degenerative intervertebral disc (IVD) has been hypothesized to contribute to back pain, but a better understanding of the interactions between the degenerative IVD and nociceptive neurons innervating the disc and treatment strategies that directly target these interactions is needed to improve our understanding and treatment of back pain. We investigated degenerative IVD-induced changes to dorsal root ganglion (DRG) neuron activity and utilized CRISPR epigenome editing as a neuromodulation strategy. By exposing DRG neurons to degenerative IVD-conditioned media under both normal and pathological IVD pH levels, we demonstrate that degenerative IVDs trigger interleukin (IL)-6-induced increases in neuron activity to thermal stimuli, which is directly mediated by AKAP and enhanced by acidic pH. Utilizing this novel information on AKAP-mediated increases in nociceptive neuron activity, we developed lentiviral CRISPR epigenome editing vectors that modulate endogenous expression of AKAP150 by targeted promoter histone methylation. When delivered to DRG neurons, these epigenome-modifying vectors abolished degenerative IVD-induced DRG-elevated neuron activity while preserving non-pathologic neuron activity. This work elucidates the potential for CRISPR epigenome editing as a targeted gene-based pain neuromodulation strategy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.