Anti-AAV Monoclonal antibody

Adeno-associated virus (AAV) was first discovered during the laboratory preparation of adenovirus preparations and has been widely used in gene therapy drug delivery as its basic biological properties have been gradually resolved. AAV is usually in a silent state after infection of the host cell and self-replicates only in the presence of helper viruses. It can transduce dividing and non-dividing cells and is expressed in non-dividing cells for long periods of time. AAV consists of an icosahedral protein capsid with a diameter of about 25 nm, containing a single-stranded DNA genome of about 4.7 kb inside. The genome has T-shaped inverted terminal repeats (ITRs) at both ends, which serve as origin and packaging signals for viral replication. The two ITRs contain the REP and CAP genes in the middle. The REP genes are responsible for encoding proteins required for viral replication and regulation, and the CAP genes are responsible for encoding capsid proteins. AAV contains multiple serotypes, and different serotypes recognize surface receptors on different cell types, thus presenting different degrees of eosinophilia.

Early research on AAV provided the basis for engineering modifications and applying AAV as a gene delivery vector. The gene GOI plasmid was modified by replacing sequences in the middle of the ITR at both ends of the AAV genome with a gene therapeutic element. The original REP and CAP genes were individually cloned into new eukaryotic expression vectors and co-transfected into eukaryotic cells as a capsid plasmid (Rep/Cap plasmid) together with a helper virus expression plasmid (Helper plasmid). In this way, a new recombinant AAV (rAAV) with the target gene sequence can be self-assembled in eukaryotic cells.

Figure 1. rAAV vectors for systemic delivery
(Source: Marino M, et al. 2022)

Numerous basic studies and clinical programs have demonstrated the high safety and delivery efficiency of rAAV. rAAV's excellent safety profile has greatly expanded its application in gene therapy. Despite the advantages of AAV such as low immunogenicity, non-pathogenicity, and the ability to transduce dividing and non-dividing cells in a variety of tissues, its entry into the body triggers varying degrees of immune responses. The AAV capsid, genome, and transgenic proteins may first trigger an innate immune response including the complement system; subsequently, activation signals recruit antigen-presenting cells, T cells, and B cells to mediate the generation of adaptive immunity. Pre-existing anti-AAV capsid-neutralising antibodies are present in most populations, and these antibodies may also impede AAV transduction to target cells, thereby affecting the efficacy of gene therapy.

Anti-Adeno-associated virus Monoclonal antibody