Fig. 1

Delivery routes in in-vivo GT approaches for MPS. Approaches for in-vivo GT of MPS may employ two different routes of viral vector administration. In direct central nervous system (CNS) administration routes, the viral vectors access the CNS via parenchyma (intracerebral injections) or via cerebrospinal fluid (CSF) (intrathecal/intraventricular injections). CNS is primarily targeted by these approaches. However, leakage of vectors in the bloodstream may result in the targeting and correction of somatic organ pathology. CNS direct approaches are generally invasive for clinical purposes. The second group of approaches is instead based on systemic injections (often directly into the blood stream) of viral vectors. These approaches efficiently target somatic organs and tissues. However, different strategies may be used to make these approaches capable of overcoming the blood–brain barrier (BBB) obstacle and treat the brain. Systemic approaches are minimally invasive and, in principle, more suitable for clinical purposes