Table 5 Tropism, advantages and safety concerns of clinically approved or NMD-relevant AAV serotypes
Serotype | Tropism towards the CNS and/or muscle | Key advantages | Safety concerns | FDA-approved drugs (brand name; year)/disease |
|---|---|---|---|---|
AAV2 | Both | Well-studied, safe for retina and CNS | Prevalence of neutralizing antibodies, immune activation | Voretigene neparvovec-rzyl (Luxturna; 2017)/biallelic RPE65 mutation-associated retinal dystrophy |
AAV5 | Both | Lower immune reactivity | Dose-related liver toxicity | Etranacogene dezaparvovec-drlb (Hemgenix; 2022)/hemophilia B Valoctocogene roxaparvovec-rvox (Roctavian; 2023)/adults with severe hemophilia A |
AAV6 | Muscle | Effective for muscle transduction | Mild immune activation | na |
AAV8 | Both | Robust liver and muscle transduction | Liver toxicity at high doses | na |
AAV9 | Both | Crosses BBB, CNS and muscle targeting | Cardiac toxicity, immune activation | Onasemnogene abeparvovec (Zolgensma; 2019)/spinal muscular atrophy aged less than 2Â years |
rAAVrh74 | Muscle | Reduced immunogenicity, effective for muscle transduction | Risk of myocarditis | Delandistrogene moxeparvovec-rokl (Elevidys; 2023)/ambulatory and non-ambulatory individuals 4Â years of age and older with DMD with a confirmed mutation in the DMD gene |