Other meanings of Adeno-associated virus
Virology & gene therapy
Adeno-associated virus (AAV) is a small Dependoparvovirus with a single-stranded DNA genome and a protein capsid. Natural AAV generally requires a helper virus, such as an adenovirus or herpesvirus, to replicate; engineered recombinant AAV vectors remove viral genes and carry therapeutic or experimental DNA instead. Their comparatively low pathogenicity, broad tissue tropism, and ability to persist largely as episomal DNA have made AAV a leading platform for in vivo gene transfer, although immune responses, limited cargo capacity, and manufacturing complexity constrain its use.
AAV is a small, non-enveloped parvovirus whose icosahedral capsid encloses a single-stranded DNA genome of about 4.7 kilobases.1 The genome is flanked by inverted terminal repeats (ITRs), which are essential for genome replication and packaging. Between them lie the rep and cap gene regions: Rep proteins support replication and genome processing, while Cap proteins form the capsid and determine much of the virus's cell and tissue preference.
Wild-type AAV is classified among the Dependoparvovirus because productive replication normally depends on a coinfecting helper virus. Without such help, infection can remain latent or yield little progeny. Recombinant vectors retain the ITRs but replace most viral coding sequences with a transgene and its regulatory elements, reducing the vector's ability to replicate while preserving delivery functions.1
Recombinant AAV vectors deliver genetic instructions to cells rather than supplying a complete replicating virus. After entry, the vector genome can be converted to double-stranded DNA and persist mainly as episomal circular or concatemeric molecules, particularly in non-dividing cells; limited integration can also occur.1 This behavior supports relatively durable expression in tissues such as retina, liver, muscle, and the central nervous system.
AAV is used in laboratory studies, genome engineering, and approved gene therapies. Luxturna uses an AAV2-derived vector to deliver RPE65 to retinal cells, while Zolgensma uses an AAV9-based vector to deliver SMN1 in spinal muscular atrophy.
Vector choice is not interchangeable: capsid serotype, promoter, route of administration, dose, and target tissue jointly shape distribution and expression.
Immune responses are the central obstacle to repeated or systemic AAV treatment. Many people carry pre-existing antibodies against naturally circulating capsids, and treatment can stimulate neutralizing antibodies, complement activity, innate inflammation, or cytotoxic T-cell responses against transduced cells.1 These effects can reduce delivery, limit eligibility, and make redosing difficult.
The payload is also small: the practical capacity is roughly 4.7 kilobases, including regulatory sequences, so large genes may need truncated proteins, dual-vector strategies, or alternative platforms. High systemic doses have been associated with liver injury and other serious adverse events, making dose selection and clinical monitoring essential. AAV vectors are replication-incompetent by design, but manufacturing must control empty capsids, aggregates, residual host-cell material, and genome heterogeneity. Regulatory evaluation therefore considers both the therapeutic gene and the vector product as a whole.
AAV biology includes several details that are easy to overlook. The ITRs are the only viral sequences normally required in a recombinant genome, while the Rep and Cap genes are supplied separately during production; this separation helps prevent generation of replication-competent vector. Capsid engineering can alter receptor binding, tissue tropism, intracellular trafficking, and antibody recognition, but laboratory improvements do not automatically translate into better human performance.
AAV genomes can persist for years in long-lived, non-dividing cells, yet expression may decline in proliferating tissues as episomal DNA is diluted. The same capsid can behave differently according to species, age, route, dose, and pre-existing immunity. AAV is also a useful research tool for cell-type-specific expression: promoters and regulatory elements can restrict transgene activity to selected neuronal, hepatic, retinal, or muscular populations. These properties make AAV versatile, but they also require careful interpretation of animal studies and long-term follow-up in patients.1
AAV terminology can refer to naturally occurring viruses, recombinant vector particles, or the broader vector platform; this entry focuses on the virus and its use as a gene-delivery vector.
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