Adeno‑Associated Virus 5 (AAV5) is a human serotype of adeno‑associated virus. It has a non‑enveloped icosahedral capsid about 25 nm in diameter and a single‑stranded DNA genome of roughly 4.7 kb. AAV5 binds to terminal sialic acid on host cells and uses the adeno‑associated virus receptor (AAVR) and platelet‑derived growth factor receptor (PDGFR) as co‑receptors, conferring natural tropism for the central nervous system, lungs and retina.
Explanation
AAV5 is part of the Dependoparvovirus genus and requires a helper virus, such as adenovirus or herpesvirus, for productive replication. Its genome encodes non‑structural Rep proteins and capsid proteins and is flanked by inverted terminal repeats that regulate replication and packaging. Wild‑type AAV5 infection is asymptomatic and results in episomal DNA that persists without causing disease. Compared with AAV2, AAV5 shows distinct antigenicity and is less likely to be neutralized by pre‑existing antibodies in humans. It efficiently transduces glial and neuronal cells in the brain, epithelial cells in the respiratory tract and photoreceptors and retinal pigment epithelium in the eye. These properties make AAV5 an attractive vector for gene therapy targeting the central nervous system and ocular tissues.
Clinical applications and important facts
AAV5 is the backbone of several approved gene therapies. Hemgenix, an FDA‑approved therapy for haemophilia B, uses an rAAV5 vector to deliver a hyperactive factor IX (FIX) gene, allowing patients to produce their own clotting factor and reduce bleeding episodes. Roctavian, approved in Europe and later by the FDA, employs an AAV5 vector to deliver the factor VIII gene for haemophilia A. AAV5 vectors have also been evaluated for treating Leber congenital amaurosis and other retinal dystrophies by delivering functional genes to the retina. In the central nervous system, rAAV5 has been used to deliver genes encoding neurotrophic factors and enzymes to treat conditions such as Parkinson’s disease and aromatic L‑amino acid decarboxylase deficiency. Low seroprevalence of AAV5‑specific antibodies broadens patient eligibility for these therapies. Ongoing research aims to optimize vector production and dosing to maximize efficacy while managing immune responses. AAV5 is a versatile adeno‑associated virus serotype with strong tropism for neural, pulmonary and ocular tissues. Its distinct antigenicity and demonstrated clinical success make it a prominent platform for current and future gene therapies. Related Terms: Adeno‑Associated Virus 6, Adeno‑Associated Virus 2, Adeno‑Associated Virus 8, Adeno‑Associated Virus 9, Adeno‑Associated Virus 1