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Self-complementary adeno-associated virus (scAAV) is a viral vector engineered from the naturally occurring adeno-associated virus (AAV) to be used as a tool for gene therapy. Use of recombinant AAV (rAAV) has been successful in clinical trials addressing a variety of diseases. This lab-made progeny of rAAV is termed "self-complementary" or sometimes referred to as "double stranded" (dsAAV) because the coding region has been designed to form an intra-molecular double-stranded DNA template. A rate-limiting step for the standard AAV genome involves the second-strand synthesis since the typical AAV genome is a single-stranded DNA template. However, this is not the case for scAAV genomes. Upon infection, rather than waiting for cell mediated synthesis of the second strand, the two complementary halves of scAAV will associate to form one double stranded DNA (dsDNA) unit that is ready for immediate replication and transcription. The caveat of this construct is that instead of the full coding capacity found in rAAV (4.7-6kb) scAAV can only hold about half of that amount (2.5-3.3kb).

In gene therapy application utilizing rAAV, the virus transduces the cell with a single stranded DNA (ssDNA) flanked by two Inverted Terminal Repeats (ITRs). These ITRs form hairpins at the end of the sequence to serve as primers to initiate synthesis of the second strand before subsequent steps of infection can begin. The second strand synthesis is considered to be one of several blocks to efficient infection. Additional advantages of scAAV include increased and prolonged transgene expression in vitro and in vivo, as well as "higher in vivo DNA stability and more effective circularization."

Virus Classification
Like AAV, scAAV is a member of the family Parvoviridae, commonly know as parvoviruses. These viruses are nonenveloped, single-strand DNA (ssDNA) viruses. Within Parvoviridae, scAAV further belongs to the Dependovirus genus, characteristically defined by an inability to replicate on their own. In nature, these viruses depend on another virus to provide replication machinery; adeno-assoicated virus can only replicate during an active infection of adenovirus. In lab use, this obstacle is overcome by addition of the helper plasmids, which exogenously expresses replication genes which AAV itself lacks.

Viral Packaging
Despite the fact that scAAV is designed to form dsDNA upon infection, the two complementary strands are not packaged in a double stranded manner. Parvoviruses package their viral genome such that the ssDNA bases come in contact with the amino acids on the inside of the viral capsid. Thus the sequence of scAAV is likely unwound by a virally encoded DNA helicase before being packaged into viral protein capsid.