The table below summarizes the relative consensus transduction potency (high/moderate/low/very low/none) of 14 commonly used capsids upon IV systemic administration in adult C57BL/6 mice, along with representative quantitative data and notes on route of administration. Because there are too many tissue columns in 14 capsids × 17, it is split into three sub-tables based on system periphery, CNS and retina, and lung/skin/bone. Key sources: Zincarelli 2008 (IV mouse types 1-9 head-to-head) [10-26]; Yang et al. 2024 (21 capsid barcode library, C57BL/6/BALB/c/cynomolgus monkey IV, 5×10¹² vg/kg) [10-27]; Bish 2008 (heart) [10-28]; Halbert 2001 (Lung) [10-29]; Chan 2017 (PHP.eB) [10-21]. Intensity is a relative qualitative judgment, with quantitative/pathway remarks in parentheses, which cannot be directly extrapolated across studies;
Sub-table A | System and peripheral tissue (IV mainly throughout the body)
|
Capsid |
Liver (liver cells) |
Skeletal Muscle |
Myocardium |
Kidney |
Pancreas |
Fat |
Tumor/Endothelial |
|
AAV1 |
Mid (IV) |
High (IV/IM)[10-26] |
High (IV)[10-28] |
Low |
Low |
Low |
Low |
|
AAV2 |
High (IV, but lower than 8/9)[10-26] |
Low-Medium (IM Medium) |
Low-Medium |
Low |
Medium (partial) |
Low |
Medium (tumor model) |
|
AAV3B |
High (hepatic hematopoietic progenitor cell preference)[10-9] |
Low |
Low |
Low |
Low |
Low |
High (HCC/hematopoietic) |
|
AAV4 |
Low (off-target in liver, consistent across species)[10-27] |
Low |
Low |
High (glomerulus)[10-27] |
High (islet)[10-27] |
medium |
Low |
|
AAV5 |
medium |
Medium(IM) |
medium |
Low |
medium |
Low |
Low |
|
AAV6 |
Medium-High (IV)[10-26] |
Medium-high (IM, may be accompanied by myositis) |
High (excellent system heart) [10-34] |
Low |
Medium (acinus)[10-27] |
Low |
Low |
|
AAV7 |
High (IV, high expression group)[10-26] |
High (IV)[10-26] |
High (IV)[10-28] |
Low |
Low |
Low |
Low |
|
AAV8 |
One of the highest (IV, conserved across species)[10-26][10-35] |
High (IV/IM) |
High (IV, slightly lower than 9)[10-28] |
Medium-High[10-35] |
Medium (acinus)[10-27] |
Low |
Low |
|
AAV9 |
High (IV, liver is still the largest reservoir)[10-26] |
High (IV, whole body muscle fiber) [10-26] |
Highest (IV, global myocardium better than 1/6/7/8)[10-28] |
medium |
High (gastrointestinal/pancreatic)[10-27] |
High (brown fat)[10-27] |
Low |
|
AAVrh.10 |
Highest (consistent across rats/monkeys) [10-27] |
High |
High (IV, slightly lower than 9) [10-36] |
medium |
medium |
Low |
Low |
|
AAVrh74 |
High (near AAV8, effective across rat/monkey liver)[10-27] |
Highest (IV, Elevidys clinical use)[10-37][10-38] |
High (IV, slightly lower than 9) [10-36] |
Low-Medium |
Low |
Low |
Low |
|
AAV-DJ |
High (mouse liver≈AAV8/9)[10-20] |
medium |
Medium-High |
medium |
Low |
Low |
medium |
|
AAV-PHP.B |
Medium (CNS/high liver disease) |
Low-Medium |
medium |
Low |
Low |
medium |
Low |
|
AAV-PHP.eB |
Medium-high (IV, liver is still high)[10-21] |
Low |
medium |
Low |
Low |
medium |
Low |
Sub-table B｜Central Nervous System and Retina
|
Capsid |
CNS-Neuron |
CNS-Astrocyte |
Cerebrovascular/Endothelial |
Retina-RPE |
Retina-Photoreceptor |
Retina-Ganglia |
|
AAV1 |
High (ICV/local; IV low) |
Medium(ICV) |
Low |
High (SR)[10-30] |
High (SR)[10-30] |
medium |
|
AAV2 |
High (local injection; very low IV) |
Low |
Low |
High (IVT biased toward RGC)[10-31] |
Medium(SR) |
High (IVT classic)[10-31] |
|
AAV3B |
Low |
Low |
Low |
Low |
Low |
Low |
|
AAV4 |
Low (IV); tubular/subventricular zone high (ICV) |
Medium (ICV deflection membrane) |
Low |
High (SR, RPE specific)[10-30] |
Low-medium (SR) |
Low |
|
AAV5 |
Medium-High (partial, Purkinje, etc.) |
High (colloid preference)[10-32] |
Low |
High (SR)[10-30] |
High (SR)[10-30] |
medium |
|
AAV6 |
Low(IV) |
Low |
Low |
medium |
medium |
medium |
|
AAV7 |
Low(IV) |
Low |
Low |
medium |
medium |
Low |
|
AAV8 |
Low (IV trace; locally high) |
Low |
Low |
High (SR)[10-31] |
High (SR, stronger than AAV2)[10-31] |
medium |
|
AAV9 |
Medium (IV; high neuron in newborns, weak in adults)[10-25] |
Medium (adult partial gelatin)[10-25] |
Low (IV is weak across BBB) |
Medium-High (SR) |
High (SR) |
Medium(IVT) |
|
AAVrh.10 |
Mid (IV) |
Low-Medium |
Low |
medium |
medium |
medium |
|
AAVrh74 |
Low-Medium |
Low |
Low |
medium |
medium |
Low |
|
AAV-DJ |
Low(IV) |
Low |
Low |
High (RPE preference)[10-39] |
medium |
medium |
|
AAV-PHP.B |
The highest (IV, only C57BL/6 series, > dozens of times AAV9) [10-22] |
High (IV, gelatinous) |
High (brain endothelial crossing) |
Low |
Low |
Low |
|
AAV-PHP.eB |
Highest (IV, 1×10¹¹vg transduces 69% cortical/55% striatal neurons)[10-21] |
High (IV)[10-21] |
High (brain endothelium) |
Low |
Low |
Low |
Sublist C｜Lung, skin, bone/cartilage
|
Capsid |
Lung-airway epithelium |
Lung-Alveoli |
Skin |
Bone/Cartilage |
|
AAV1 |
medium |
medium |
To be approved |
Low |
|
AAV2 |
Low (poor IV; partially weaker than 6)[10-29] |
Low |
To be approved |
Low |
|
AAV3B |
Low |
Low |
To be approved |
Low |
|
AAV4 |
High (local; alveolar 21.2% vs AAV9 1.7%)[10-27] |
High (IV, lung tdTomato⁺~21%)[10-27] |
To be approved |
Low |
|
AAV5 |
High (strong intracavitary administration)[10-29] |
medium |
To be approved |
Low |
|
AAV6 |
Highest (airway epithelium, about 3 times stronger than AAV2)[10-29] |
medium |
To be approved |
Low |
|
AAV7 |
Low |
Low |
To be approved |
Low |
|
AAV8 |
Low |
Low |
To be approved |
Low |
|
AAV9 |
medium |
medium |
To be approved |
Low |
|
AAVrh.10 |
Low |
Low |
To be approved |
Low |
|
AAVrh74 |
Low |
Low |
To be approved |
Low |
|
AAV-DJ |
Low |
Low |
To be approved |
Low |
|
AAV-PHP.B |
Low |
Low |
To be approved |
Low |
|
AAV-PHP.eB |
Low |
Low |
To be approved |
Low |
Matrix notes. The high CNS transduction of AAV-PHP.B/PHP.eB is strictly limited to Ly6A-permissive strains such as C57BL/6J (see 6.3), and this advantage disappears in BALB/c, CD-1, and NHP; the high CNS/retinal transduction of AAV2 is almost entirely from local injection (parenchyma, ICV, IVT), and its IV systemic administration has extremely low CNS transduction.
AAV1: Muscle/nerve excellent. IM is highly efficient in skeletal muscle, ICV/brain parenchymal neurons and ependyma are strong, SR administration is efficient in RPE and photosensitivity, IV is liver-enriched, etc.; it is often used for local administration of neuromuscular diseases and CNS [10-26][10-28][10-30].
AAV2: The most well-studied, “moderately broad-spectrum but not extreme” affinity. Local brain injection and IVT retinal RGC are classic scenarios; IV liver enrichment but less than 8/9, HSPG dependence makes it easy to be cleared by liver non-parenchymal cells combined with heparin [10-8][10-26].
AAV3B: Liver and hematopoietic/hepatocellular carcinoma bias, recognizes HSPG+HGFR; used in hepatic progenitor cells and HCC models, systemic CNS/muscle weakness [10-9].
AAV4: Consistent liver off-target + lung/alveolar/glomerular/islet preference across species; Yang 2024 showed AAV4 lung tdTomato⁺ 21.2% vs AAV9 1.7%, and this liver off-target is also true in cynomolgus monkeys [10-27]. ICV is in the ependyma, SR administration is specific to RPE (RPE65 has been used clinically); AAVR is not necessary, making it a framework for engineering low-hepatotoxicity vectors [10-12].
AAV5:N-linked α2-3 sialic acid+PDGFR. ICV/brain parenchyma is biased toward astrocytes, has high efficiency in airway luminal delivery, and strong photosensitivity/RPE in SR delivery (AAV5 used in Spark/RPGR clinical trials) [10-14][10-29][10-32].
AAV6:The only one that simultaneously binds α2-3/α2-6 sialic acid + HSPG; optimal for airway epithelium (about 3 times stronger than AAV2) [10-29], excellent for IV systemic heart [10-34], and IM skeletal muscle can be accompanied by inflammatory response [10-33].
AAV7: IV high expression group (same level as AAV9), strong in muscle/liver/heart, and low immunogenicity [10-26].
AAV8: One of the gold standards for liver targeting, IV hepatocytes are highly efficient and relatively conserved across species [10-26][10-35]; SR administration is more photosensitive than AAV2 [10-31]; muscle, heart, kidney, and pancreas can all be transduced.
AAV9: Broad spectrum + cross-BBB (strong in newborns, weak in adults) + strongest in global myocardium[10-25][10-28]. IV is high in skeletal muscle, cardiac muscle, and liver; IV in adults is weak across the BBB; SR is acceptable in all layers of the retina. Zolgensma (SMA) uses AAV9.
AAVrh.10:Isolated from rhesus monkeys, it recognizes sulfated LacNAc; the liver is consistently efficient across mice/monkeys[10-27], and the muscle/heart is high, but the measured myocardial transduction of NHP is slightly lower than that of AAV9[10-36]; MPS IIIA and other clinical uses.
AAVrh74: Closely related to AAV8 (Clade E), muscle-biased; Elevidys is used for DMD, the MHCK7 promoter drives microdystrophin [10-37][10-38]; NHP is effective in both liver and muscle [10-27].
AAV-DJ:AAV2/8/9 in vitro reassortment chimera, combined with HSPG; mouse liver ≈AAV8/9 and transduces a variety of human cells better than the parent, with RPE preference [10-39]. Note: Liver dominance is only in mice, NHP is not conserved [10-27].
AAV-PHP.B:AAV9 VR-IV inserts TLAVPFK peptide and binds Ly6A; IV extensively transduces C57BL/6J brain parenchymal neurons + glia, still high in liver, only effective in C57BL/6 line [10-22].
AAV-PHP.eB: Optimized version of PHP.B, 1×10¹¹ vg can transduce 69% cortex/55% striatal neurons, the dose can be reduced to 1/20 of PHP.B, partial to inhibitory neurons; still relies on Ly6A, strain restrictions are the same as PHP.B[10-21].