Genomic and episomal DNA (DNA)

CNS-expressed genomic and episomal DNA serves as the fundamental substrate for gene-based therapeutics within the central nervous system. Genomic DNA comprises the host's chromosomal material, while episomal DNA refers to non-integrated genetic elements, such as delivered plasmid DNA (pDNA), that exist independently within the nucleus (2). In therapeutic contexts, pDNA is delivered to CNS cells to supplement missing proteins, knock down toxic gene products, or facilitate gene editing of the host genome (3). This target is central to treating a wide array of neurological conditions, including spinal muscular atrophy and Parkinson's disease, by restoring cellular function at the genetic level (4). However, the use of pDNA in the CNS is challenged by the blood-brain barrier, the requirement for sophisticated non-viral delivery systems, and the potential for inflammatory responses to foreign DNA (1). (1) Ramamoorth, M., & Narvekar, A. (2015). Non viral vectors in gene therapy- an overview. J Clin Diagn Res. (2) Hardee, C. L., et al. (2017). Advances in Non-Viral DNA Vectors for Gene Therapy. Genes. (3) NIH/NCBI: Gene therapy for neurological disorders. (4) PubChem: Plasmid DNA.

Other names

Nuclear DNAChromosomal DNAPlasmid DNApDNAExtrachromosomal DNAHost genome

Exogenous gene expression via episomal transcription or genomic modification to supplement deficient proteins or silence pathogenic genes.