Trends in Molecular Medicine | Strategy of the Month Delivery of therapeutic AAV9 vectors via cisterna magna to treat neurological disorders Paolo M. Marchi," Lara Marrone," and Mimoun Azzouz"* "shal tte Tana Neursince [TN Depart of Neroscence, Univer feel, 3A Gceop Rl, Sees, 50/20, UK sat, ry | urs conte alo ewe CMP AAV manuacting sad a cance) Protioeeeornores] “St mast ‘cowpea = = Ny = or rman comet ’ non Sits ore 3 eerie = ‘ora eerralacmisvaon 0 cine grade acseno asobieg wus (AAV) vectors for gene tetany. The AY ‘maratctrn uy precces igh custy produ! ofwel-cned props. Fer rare clara macra (OK) etry an actalehod dose of rerapeute vis is noctod the crsbrospnal us (SF subarachrot space batnoan the cerebelsm and he dora sxe a he macula obra. ‘AVS delivery to the CNS ‘in onteatcce ‘ty (Oreron of avalabie routes for adeno-aseocated ves 9 (AAV) dla to he conta ervus sat (ONS) ‘Anatomical dave stes and ther espectve via Doct ibuon profes along the ONS are hriighted. A summary ol pros and cons ofeach delivery route reveals ICM cetvery as he rest promisng route io targot ‘heGNS his enersion, HoNever, Ono ef ak reported tht Umber pune LY can achieve ir resus, ICdtnjecton of AAV screws widespread transgene delivery in bon brain and epi cord. Tis distinct benefit ai rracreoroverror ICY) acmnstaton, wi gets tho bral TOM Ger ads to rete \ssempaten of he vctro parpberal organs (suchas the fe), as wal as bot evasion of ercuatng ans AAV nowratsinganitedes (Abs), whch re ‘ecomrised botenecs of steric AAV ate, OW oer reat sn ie ses compared wth systemic deivey, nproong salty nd eur the cos fiat yada vector manufacturing CHaLLenaes: Moderste dorsal oo ganglon (DFG) pathotog/ was reper nes oo non-human grates ar pits wth ‘mononuclear cel nates and secordayy ecnopat. JOM pot common used cic Pact ave o reese proces Fae, pcg nadvertert ny to vacear suche and trast Gamage Lumbar ivr.) mint acho ‘ir stuton neha ra a spralcor. APPLICATIONS: Cine le baead on OM nation of ‘AVA voce fr gore thorapy aro bang conde in parts with rucopeimacrandes toe ard I, Pakcrean' cease, enteral ‘ment and Gaucher oeabe pee" ‘Tha AAVD var AAV bog teste incl fected by gengicadoss" acca) artie tie ese” “conan: ramnindahiog sok QM fom, OCeIPreSs werntacte intimin iV Ne OxEIPnedovErnnlsd — enagrineimimzriensr 79