Replicationincompetent

Replication-incompetent is a descriptor used primarily in virology and gene delivery to refer to agents that cannot complete a full replication cycle within a host organism. In this context, replication-incompetence is achieved by deleting or inactivating one or more genes essential for replication or removing genomic elements required for production of infectious progeny. The modified agent can enter cells and, in the case of vectors used for gene delivery, express the payload, but it cannot produce new viral particles to spread the infection. The viable life of the vector is limited to the initial transduction event, and expression is typically transient, although some vectors can sustain longer expression depending on the system.

Applications include gene therapy, where replication-incompetent vectors deliver therapeutic genes to target tissues, and vaccines, where they present antigenic proteins without propagating illness. Several vector platforms are engineered to be replication-incompetent, including adenoviral vectors, adeno-associated virus (AAV) vectors, and lentiviral vectors; replication incompetence reduces the risk of uncontrolled spread in patients but does not eliminate all biosafety concerns.

Manufacturing and clinical use require careful screening for potential recombination events that could restore replication capability, validation of purity and potency, and adherence to regulatory oversight. Limitations include restricted payload capacity, potential immunogenicity, and transient expression with non-integrating vectors. The term is sometimes used as a contrast to replication-competent or live-attenuated agents, where some replication is allowed. See also viral vector, gene therapy, vaccine vector.