Viral Vectors 101: AAV Serotypes and Tissue Tropism

A viral vector that can target specific tissues, even when administered systemically, without causing disease? Recombinant adeno-associated viral vectors, or rAAVs, can sound almost too good to be true!

In a previous post, we covered systemic capsids, which allow AAVs to broadly spread throughout an organism, including difficult-to-target tissues like the central nervous system. In this post, we’ll dive into the opposite: AAV serotypes with varying tissue tropism, allowing them to target particular cell types.

Figure 1: Diagram of AAV components. Created with BioRender.com.

AAV vectors have both distinctive capsids and genomic structures. The viral capsid is the key that lets AAVs “unlock” and infect specific cells. This protein shell packages the vector’s genetic material, and variations between serotypes can change how the viral particle sneaks its way into cells. Generally, AAV serotypes have a primary cellular receptor and sometimes one or multiple coreceptors, which may be present on different cell types and sometimes vary between target species or even strains.

Pro tip! Getting a vector into a particular cell type depends largely on the viral capsid, but specificity doesn’t end there: expression from rAAVs also depends on your choice of promoter/enhancer.

Table 1: AAV capsids and receptors.

Capsid	Primary receptor	Coreceptor
AAV1	α2,3-/α2,6 N-linked sialic acids1 AAV receptor (AAVR)2
AAV2	Heparan sulfate proteoglycan (HSPG)3 AAV receptor (AAVR; not strictly required)2	Human fibroblast growth factor receptor 1 (FGFR1)3 αVβ5 and α5β1 integrins3 Hepatocyte growth factor receptor (HGFR)3 Laminin receptor (LR)3 CD93
AAV5	2,3-N-linked sialic acid4 AAV receptor (AAVR)2	Platelet-derived growth factor receptor (PDGFR) α and β3
AAV6	α2,3-/α2,6 N-linked sialic acids1 Heparan sulfate proteoglycan (HSPG)3 AAV receptor (AAVR)2	Epidermal growth factor receptor (EGFR)3
AAV8	Laminin receptor (LR)3 AAV receptor (AAVR)2 Carboxypeptidase D (CPD), also called AAVR25
AAV9	Terminal N-linked galactose3 AAV receptor (AAVR)2	Laminin receptor (LR)3 Putative integrin3
AAV11	Carboxypeptidase D (CPD), also called AAVR25

¹Wu, Miller, et al., 2006
²Pillay et al., 2016
³Issa et al., 2023
⁴Kaludov et al., 2001; Walters et al., 2001
⁵Dhungel et al., 2025

Depending on how you count, there are up to thirteen natural serotypes of AAV identified so far, numbered AAV1, AAV2, and so on. In addition, researchers have created many engineered serotypes by mixing, matching, and modifying capsid and genomic structures. For example, rAAV pseudotypes mix the genome of one AAV serotype with the capsid of another. Formally, pseudotypes are described with two numbers separated by a slash: the first number refers to the genome, and the second number to the capsid.

Most vectors provided by Addgene are pseudotypes using the genomic structure of AAV2, so they are formally called rAAV2/1, rAAV2/2, and so on, although we often use abbreviated nomenclature (AAV1, AAV2, etc.) to distinguish the capsids from one another.

Common serotypes

We’ll cover the most commonly used serotypes in this post. However, tissue tropism varies both between species and even between strains of one species, so be sure to check the literature and validate your choice of AAV vector for your experimental system.

Table 2: Availability of AAV serotypes at Addgene.

Serotype	In-stock viral prep	Packaged on Request
AAV1	✓	✓
AAV2	✓	✓
AAV2-retro (AAVrg)	✓	✓
AAV5	✓	✓
AAV6	✓	✓
AAV8	✓	✓
AAV9	✓
AAV11	✓	✓

AAV1

AAV1 was the first viral vector approved for gene therapy (Issa et al., 2023). It may be a good choice for targeting neurons, with high transduction frequencies in the central nervous system (CNS) (Wu, Asokan, et al., 2006). AAV1 has also been found to transduce skeletal muscle, cardiac, and retinal cells (Issa et al., 2023).

AAV2

Despite being isolated second, AAV2 is the best studied and most commonly used serotype. Its genome is the most common choice for AAV pseudotyping. It has broad tissue tropism, including liver, muscle, lung, CNS, kidney, retinal, and pancreatic cells (Ahuja et al., 2025; Issa et al., 2023; Wu, Asokan, et al., 2006).

AAV2-retro (also known as AAVrg)

We’ve covered AAVrg in a previous blog post, but to summarize briefly: AAVrg is derived from AAV2 and engineered to infect neurons and undergo retrograde transport, traveling up the axon to the cell body and driving transgene expression (Tervo et al., 2016). This functionality makes it useful for mapping neural connections.

Although derived from AAV2, AAVrg has not been thoroughly studied in contexts outside the nervous system to confirm its cellular receptors and tissue tropism.

AAV5

AAV5 is the most genetically distinct AAV. Though AAV5 is one of many serotypes used to target the central nervous system, including neurons, AAV5 is generally the best choice for targeting astroglia. It has additionally been reported to have tropism for liver, vascular endothelial, and smooth muscle cells (Issa et al., 2023).

AAV6

AAV6 is thought to be a natural hybrid of AAV1 and AAV2, with only six amino acids distinguishing its capsids from those of AAV1 (Issa et al., 2023; Wu, Asokan, et al., 2006). AAV6 is particularly well-suited for transduction of lung cells via airway administration (Halbert et al., 2001). It additionally has tropism for cardiac and liver cells (Issa et al., 2023), as well as skeletal muscle, although muscle inflammation and degeneration has been reported (Muraine et al., 2020).

AAV8

AAV8 has high transduction efficiency in multiple tissues, rapid transgene expression, and can cross blood vessel barriers. It is especially popular for applications targeting liver tissue. In addition, it has been shown to transduce skeletal muscle, cardiac, pancreas, smooth muscle, CNS, kidney, and retinal cells (Issa et al., 2023; Wu, Asokan, et al., 2006).

AAV9

AAV9 has relatively broad tissue tropism and high transduction efficiency, and is an excellent choice for targeting cardiac cells (Bish et al., 2008). It can also cross the blood-brain barrier, making it useful for applications targeting the CNS (Issa et al., 2023). Additionally, AAV9 has been shown to transduce liver, skeletal muscle, pancreatic, and retinal cells (Issa et al., 2023).

AAV11

AAV11 is a relatively recent addition to the toolbox, with the first paper identifying a binding receptor published this year (Dhungel et al., 2025)! It can transduce neurons for retrograde labeling, as well as astrocytes in the CNS (Han et al., 2023), and has also been reported to have tropism for liver and kidney cells (Issa et al., 2023).

In summary

Your choice of AAV vector inherently depends on the design of your experiment. Though we cannot make universal serotype recommendations, the following table summarizes tissue tropism as we currently understand it. Tropism depends on many variables, so be sure to check the literature for previous work in your experimental system.

Table 3: AAV tissue tropism.

To target...	Try using...
CNS	AAV1, AAV2, AAV2-retro (AAVrg), AAV5, AAV8, AAV9, AAV11
Heart	AAV1, AAV8, AAV9
Kidney	AAV8
Liver	AAV8, AAV9
Lung	AAV6
Pancreas	AAV2, AAV8
Photoreceptor cells	AAV2, AAV5, AAV8
Skeletal muscle	AAV1, AAV8, AAV9

In addition to tissue tropism, different AAV serotypes can be useful to evade neutralizing antibodies developed from prior natural exposure or rAAV treatment, which can pose problems for gene therapy applications. Cross-reactivity of AAV serotypes varies by species and route of administration (Wu, Asokan, et al., 2006).

Want to know if a capsid is a good option for your experiment? Use Addgene’s AAV Data Hub to find experimental reports on commonly used vector cargo designs and administration doses. Don't forget to submit your validation data after your experiment!