TBG-SaCas9HF AAV (Serotype 9)

TBG-SaCas9HF AAV (Serotype 9) utilizes the liver-specific TBG (thyroxine binding globulin) promoter to drive the expression of SaCas9HF. SaCas9HF is a highly precise genome editing enzyme that is smaller in size than the more commonly used SpCas9. This compact nature makes SaCas9HF more compatible with AAV vectors with limited packaging capacity, thereby maximizing its potential for therapeutic applications. AAV serotype 9 was specifically selected as this delivery system due to its ability to efficiently transduce multiple tissues in vivo, with particular affinity for the central nervous system and liver. This serotype is able to cross the blood-brain barrier and tropism for cardiac and skeletal muscle, making it a valuable tool in gene therapy, especially for the treatment of systemic diseases and dysfunctions that affect multiple organ systems.

TBG (Thyroxine binding globulin) is a 54 kDa acidic glycoprotein specifically expressed in the liver, whose main function is to bind and carry thyroid hormones in the circulation. TBG as an AAV promoter enables long-term and sustained overexpression in hepatocytes. TBG specifically causes low expression of the target gene or interfering sequence in other tissues, which can reduce the impact on other tissues and organs, while also reducing toxicity or immunogenicity to other organs and reducing experimental interference. Compared with commonly used broad-spectrum overexpression promoters, the overexpression efficiency of TBG in hepatocytes is comparable to that of CMV and CAG.