AAV8 Empty Capsids

Adeno-associated virus (AAV) is one of the most promising gene therapy vectors and a powerful tool for delivering target genes. Compared with other vector tools, AAV carries genes that can survive for a long time in the patient's body and does not lead to potential insertional mutations in the host cell genome, thus improving the safety of gene therapy. In addition, different AAV serotypes have specific affinities for different tissues and can therefore be used for therapeutic design in different target organs. Among them, AAV serotype 8 (AAV8) has attracted a lot of attention because of its efficient and stable gene transfection of specific tissues, and recombinant AAV8 has been widely used in gene therapy research for a variety of diseases, including genetic diseases, cancers, and autoimmune diseases.

AAV is a single-stranded DNA virus whose overall structure consists of two parts: an icosahedral protein capsid with a diameter of about 26 nm and a single-stranded DNA genome with a length of 4.7 kb. The capsid contains three types of viral proteins (VPs), including VP1, VP2, and VP3. The structure of the ordered region of the AAV8 VP monomer consists of an eight-stranded β-barrel motif at the core and long loops between the strands, including the HI loop (the loop between βH and βI), αA, and a loop region that forms a protrusion around the icosahedral triad (pL1 to pL3). Variable region I of AV8 has two and five more amino acids than the same region in AAV2 and AAV4, respectively. Variable region II is located at the transition between the β-bands, forming a five-fold axial channel, while variable region IV is located in the macrocycle region between βG and βH of the β-chain (called the GH loop). AAV8 was isolated from rhesus monkey tissues and is highly homologous to other AAVs, with AAV8 and AAV2 showing the highest structural similarity of 83% in capsid structure. Crystal structure analysis revealed that AAV8 and AAV2 viruses have different capsid surface topologies. the primary receptor for AAV2 is heparan sulfate proteoglycan, whereas AAV8 has no affinity for heparan sulfate, and the 37/67-kDa laminin receptor (LamR) is believed to be the host cell receptor for AAV8.

Figure 1. AAV8 virus structure
(Source: Zhao L, et al. 2023)

Recombinant AAV vectors are safe, capable of transfecting a wide range of host cells, and can effectively mediate the long-term stable expression of exogenous genes in a variety of cells without expressing any viral protein genes. Currently, AAV8 has been used in preclinical and clinical stage studies of many diseases. Long-term correction of hemophilia A, familial hypercholesterolemia, and type II glycogen storage disease was achieved using AAV8 as a gene therapy vector in a mouse model. In addition, AAV8 liver-targeted gene therapy was successfully demonstrated in a canine model. Successful targeting of this vector in the mouse pancreas has also been reported.

AAV serotype 8 Empty Capsids
Adeno-associated virus 8 Empty Capsids
Adeno-associated virus type 8 Empty Capsids