Engineered Exosome‑Based siRNA Delivery Targeting Epstein–Barr Virus Latency in Multiple Sclerosis: A Model for Antiviral Neurotherapeutics

Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative disorder of the central nervous system (CNS) with unclear upstream etiology. Accumulating evidence implicates Epstein–Barr virus (EBV) as a necessary antecedent for MS in most cases, via lifelong latency in B cells and occasional reactivation that perturbs immune tolerance and fosters neuroinflammation. Current MS therapies predominantly modulate immunity without addressing viral reservoirs. We propose a translational platform that engineers blood–brain‑barrier (BBB)‑permeant exosomes to deliver small interfering RNA (siRNA) against EBV latency determinants (e.g., EBNA1, LMP1). The central hypothesis is that sustained knockdown of these transcripts in EBV‑positive B cells and glial targets will (i) reduce viral persistence/reactivation, (ii) blunt downstream inflammatory cascades driving demyelination, and (iii) slow disability progression. We outline a stepwise program spanning in‑silico siRNA design, exosome surface ligand engineering for B‑cell/CNS tropism, rigorous in‑vitro and in‑vivo validation, biodistribution/tox studies, and an adaptive preclinical efficacy trial. If successful, this work establishes a generalizable antiviral neurotherapeutic framework.​