Adeno-associated virus (AAV) is currently the most commonly used in vivo gene therapy vector and has been approved for the treatment of a variety of diseases including retinitis pigmentosa, spinal muscular atrophy, Duchenne muscular dystrophy and hemophilia.
The clinical success of these human gene therapies depends on whether adeno-associated virus (AAV) can be safely and effectively transduced into a variety of tissues. However, dose-related toxicity and even death, as well as high-dose-related significant attenuation of transgene expression, have prompted people to deeply understand the molecular mechanism of AAV-host interaction.
Recently, researchers from Peking University and the University of Sydney published a research paper entitled "An alternate receptor for adeno-associated viruses" in the international top academic journal Cell. The study discovered an alternative receptor for adeno-associated virus (AAV) - AAVR2 (CPD), which can restore the transduction of E-branch AAV (including AAV8) in the absence of AAVR, and provides an exclusive entry channel for unclassified AAV11 and AAV12 that is independent of AAVR. In addition, the research team overexpressed a minimal functional AAVR2 (miniAAVR2) to enhance AAV transduction in vivo, allowing low doses of AAV to achieve similar therapeutic effects.
Figure 1. AAVR2 is an alternate receptor for adeno-associated viruses. (Dhungel B P, et al., 2025)
Currently, AAV serotypes can be divided into six branches (A to F) based on the amino acid sequence and structure of their capsids. Different serotypes can target different tissues/disease groups because they exhibit different cell/tissue tropisms. A major difference between different serotypes of AAV is the affinity of their capsids for host proteins, including receptors that regulate transduction and tissue tropism. For example, AAV8, a widely used vector for human gene therapy, has a structure that is 94% similar to the earliest discovered serotype AAV2, but has differences in immunogenicity, receptor binding, and tissue tropism.
| Cat.No. | Product Name | Price |
|---|---|---|
| AAV00084Z | AAV (Serotype 5) | Inquiry |
| AAV00078Z | AAV (Serotype 2) | Inquiry |
| AAV00104Z | AAV (Serotype 9) | Inquiry |
| AAV00091Z | AAV (Serotype 6) | Inquiry |
| AAV00097Z | AAV (Serotype 8) | Inquiry |
| AAV00079Z | U6-shRNA-GFP AAV (Serotype 2) | Inquiry |
| AAV00081Z | mRFP AAV (Serotype 2) | Inquiry |
| AAV00102Z | CAG-ChR2-YFP AAV (Serotype 8) | Inquiry |
| AAV00109Z | CAG-ChIEF-tdTOMATO AAV (Serotype 9) | Inquiry |
| AAB0007 | CMV-iGluSnFR AAV (Serotype 8) | Inquiry |
| AAB0013 | pRSET.GCaMP5G(7.35) AAV (Serotype 9) | Inquiry |
| AAB0042 | CAG-FLEX-NES-jRCaMP1b AAV (Serotype 9) | Inquiry |
| AAB0047 | CAG-FLEX-jGCaMP7b AAV (Serotype 9) | Inquiry |
| AAV00325Z | Syn-GFP AAV (Serotype Retrograde) | Inquiry |
| AAV00329Z | Syn-Cre-mCherry AAV (Serotype Retrograde) | Inquiry |
In this latest study, the research team reported an alternative receptor for AAV, AAVR2, or carboxypeptidase D (CPD), which is different from the multi-serotype AAV receptor (AAVR).
AAVR2 mediates transduction of clade E adeno-associated viruses (AAVs), including AAV8, and identifies a unique AAVR-independent transduction pathway for unclassified AAV11 and AAV12. The team characterized direct binding between AAV8 capsid and AAVR2 by cryo-electron microscopy (cryo-EM) and identified the contacting amino acid residues. The team observed that AAV8 directly binds to the carboxypeptidase-like domain-1 of AAVR2 through its variable region VIII and demonstrated that AAV capsids lacking AAVR2 binding capacity can be bioengineered to interact with AAVR2. Finally, the team overexpressed a minimal functional AAVR2 (miniAAVR2) to enhance AAV transduction in vivo, allowing low doses of AAV to achieve similar efficacy.
Overall, this study provides new insights into AAV biology and offers clinically applicable solutions to reduce dose-related toxicity associated with AAV vectors.
Reference
Dhungel B P, et al. An alternate receptor for adeno-associated viruses. Cell, 2025.