Using Herpes Simplex Virus Type-1Based Amplicon Vectors for Neuroscience Research and Gene Therapy of Neurological Diseases

ALBERTO LUIS EPSTEIN; ALEJANDRA INES AGUIRRE; MARIA VERONICA BAEZ; DIANA ALICIA JERUSALINSKY

Molecular-Genetic and Statistical Techniques for Behavioral and Neural Research

Academic Press-Elsevier

Lugar: Londres; Año: 2018; p. 445 - 477

Herpessimplex virus type-1 (HSV-1) based vectors are strongly neurotropic, especiallyin vivo. Amplicons are defective,helper-dependent HSV-1 vectors that allow efficient infection of many neuronaltypes, with relatively long-term transgene expression, without evident sideeffects. They share features of wild type HSV-1, as the ability to infect severaldividing and non-dividing cells. The main interest of amplicons is that theirgenome does not carry protein-encoding viral sequences and remains episomal,avoiding risk of insertional mutagenesis, features that make them completelysafe for the host and non-toxic for the cells. The absence of virus genesprovides space for large DNA sequences (150-kbp), allowing to deliver completegene loci, including introns, exons, and long regulatory sequences, conferringtissue-specific expression or stable maintenance/expression. Two methodologieshave been developed to generate helper-free amplicons or faintly contaminatedwith defective helper particles, with larger titles. We summarize thesemethodologies and the use of amplicon vectosfor basic research in neuroscience(neurotrophins, neurorreceptors, and other molecules roles in behavior), andfor experimental gene therapy of neurological disorders (ataxias, Parkinson andAlzheimer diseases, epilepsy, auditory system deficits, ischemia,neurotoxicity, neuropathic pain).