F8 and hemophilia A: Theoretically, full-length F.VIII could be ligated into a single optNE-DNA construct and provide disease remediation for those that suffer from hemophilia A. This is currently an issue for standard AAV therapy, even when using the truncated B-domain deleted hF.VIII gene, because the length of the gene cassette (~5.0 kb) is larger than the carry capacity of AAV (~4.7 kb) (Roberts et al., 2011).