Monoclonal antibodies recognising Adeno-associated virus (AAV)
Adeno-associated viruses A(AAV), a member of the parvovirus family, are small single-stranded DNA viruses that infect humans and some non-human primate species. Currently, 13 human and non-human primate AAV serotypes and 150 genotypes have been reported. AAV is currently considered to be non-pathogenic and most people infected with AAV only develop a mild immune response. Adeno-associated virus capsids carry genes into both dividing and quiescent cells where they can insert genetic information into the host genome.
The different AAV serotypes have been shown to demonstrate tropism for specific tissues and cell types. This is due to the variations in their amino acids sequences and capsid structure, which enables them to interact with different host cell receptors. These characteristics of AAV have been exploited for gene therapy and recombinant AAV virus have been engineered to carry therapeutic genes into a diverse range of host cells.
Various clinical trials are currently ongoing which utilise different AAV serotypes including:-
- AAV1 has been reported to show enhanced tropism for skeletal muscle, heart muscle, retinal pigment epithelium and the central nervous system (CNS). AAV1 is currently used in clinical trial studies for alpha-1 antitrypsin deficiency, limb girdle muscular dystrophy, Duchenne muscular dystrophy and heart failure therapy.
- AAV2 demonstrates tropism in kidney tissue, retinal pigment epithelium, photoreceptors and the CNS. AAV2 is currently used in clinical trials studies for a wide range of conditions including hemophilia B, Duchenne muscular dystrophy, Parkinson’s disease, age-related macular degeneration, choroideremia and rheumatoid arthritis.
- AAV5 demonstrates tropism for retinal pigment epithelium, photoreceptors, lung tissue, and the CNS. AAV5 is currently used in clinical trial studies for hemophilia B and rheumatoid arthritis gene therapy.
- AAV6 demonstrates tropism for skeletal muscle and lung tissue. AAV6 has been used in clinical trials for the treatment of severe heart failure.
- AAV8 demonstrates tropism for a wide range of tissues including liver, pancreas, skeletal muscle, heart and CNS. AAV8 is currently used in clinical trials for a range of conditions including hemophilia A, hemophilia B, X-linked myotubular myopathy and hepatitis C gene therapy.
- AAV9 demonstrates tropism for skeletal muscle, heart, liver, lung and the central nervous system. AAV9 is currently used in clinical trial studies for Pompe disease, Batten disease and spinal muscular atrophy gene therapy.