Double-Stranded scAAV vectors (Next Generation Vectors) The double-stranded AAV genome is generated by mutating the terminal resolution site sequence on one side of the inverted terminal repeats (ITR), leading to the production of self-complementary AAV (scAAV). A genome <2.5 kilobases (kb; approximately half the size of the wild-type AAV genome) can therefore be packaged as a dimer in the AAV vector with the package size limit of 4.7kb. Advantages of scAAV vector design A single-stranded AAV viral vector is widely used for gene therapy. Upon transduction, the single-stranded DNA must be converted into a transcriptionally active double-stranded form, which is a crucial rate-limiting step in transgene expression from an rAAV vector. With a scAAV double-stranded vector design, the synthesis of the complementary strand is not required. Double-stranded scAAV is less prone to DNA degradation after viral transduction, thereby increasing the number of copies of stable episomes Doub...