Table 2.
List of pre-clinical studies for AAV- and LV-mediated targeting of glial cells in the central nervous system.
| Viral vector | Cell target | Route of administration | Animal/cell models | Transduction efficiency | References |
|---|---|---|---|---|---|
| AAV6-gfaABC1D-EGFP-miR124T | Astrocytes | Primary cortical cells from embryonic day 18 rat pups. | gfaABC1D promoter was not selective for astrocytes in vitro (66.9 ± 11.1% astrocytes and 33.1% neurons). | Taschenberger et al., 2017 | |
| IS | Young adult female Wistar rats | miR-124 detargeted transgene neuronal expression in vitro and in vivo, but lower transduction efficiency has been reported. | |||
| AAVDJ8-GFAP-mCherry | Primary cortical neurons and mixed glia from P0 neonatal C57BL/6 mice | Astrocytes: 83.2% ± 6.5 mCherry+/GFAP+ cells (primary cortical cultures). | Hammond et al., 2017 | ||
| ICV | P0 neonatal C57BL/6 mice. | Astrocytes: 80.3 ± 6.3 mCherry+/S100β+ cells (3 weeks post-injection). | |||
| AAV2/5-CBA-EGFP | ICV | Neonatal (p0, p2, and p3) B6C3F1/Tac mice | Time- and serotype-dependent distribution: AAV2/8 and AAV2/9 displayed the widest tissue distribution. | Chakrabarty et al., 2013 | |
| scAAV9-CBA-GFP | IV | Neonatal and 70-day-old C57Bl/6 mice | Neuronal and astrocytes transduction in neonates. 90% of astrocytes transduction in adult spinal cord. |
Foust et al., 2009 | |
| rAAV-dsCAG-GFP (ShH19, ShH13, and L1-12 capsids) | Astrocytes, Müller cells | IS, subretinal area | Adult Fischer rats, adult Sprague Dawley rats | ShH19 and L1-12 transduced 5.5-fold (14.9 ± 3.0%) and 3.3-fold (9.0 ± 3.0%) higher numbers of astrocytes compared to AAV2 | Koerber et al., 2009 |
| rAAV2-RSV-βgal rAAV4-RSV-βgal rAAV5-RSV-βgal |
Astrocytes, Neurons | IS, ICV | 6/8-week-old C57BLy6 mice | Higher transduction efficiency of rAAV4 and rAAV5 in the striatum (15 weeks post-injection). Higher transduction efficiency of rAAV5 in the ventricle (3 and 15 weeks post-injection). |
Davidson et al., 2000 |
| AAV4-RSV-βgal | IV, SVZ | Newborn and young adult C57BL/6 mice | Low number of NeuN+ cells in the OB (IV). High GFAP+ cells in the OB (SVZ). |
Liu et al., 2005 | |
| AAV-PHP.eB AAV-PHP.S |
IV | 6/8-week-old C57BL/6J mice | AAV-PHP.eB transduced 69% of cortical and 55% of striatal neurons. AAV-PHP.S transduced 82% of dorsal root ganglion neurons, as well as cardiac and enteric neurons |
Chan et al., 2017 | |
| AAV2-CMV-GFP (hu.32, hu.37, hu.11, pi.2, hu.48R3, and rh.8 capsids) | Astrocytes, Oligodendrocytes | ICV (neonatal), IP (adult) | Neonatal and adult C3H/HeOuJ mice | Higher transduction efficiency of hu.11 (4.54% ± 2.19 GFP positive area). hu.32 and hu.48R3 led to GFP expression in astrocytes. |
Cearley et al., 2008 |
| bdLV.GALC.GFP | EC | FVB/Twitcher mice | 3% of astrocytes (GFAP+), 8% of oligodendrocytes (APC+), and <2% macrophages/microglia (CD68+ and Iba1+ cells). | Lattanzi et al., 2014 | |
| LV.hARSA LV.GFP |
Astrocytes, Oligodendrocytes, Neurons | IP | Macaca fascicularis | 22.3 ± 5.7% of astrocytes (GFAP+), and 24.4 ± 10.6% (CNPase+), 50.5 ± 5.7% of neurons (NeuN+) | Meneghini et al., 2016 |
| AAVrh.10-CAG-cuARSA | Oligodentrocytes | IS, IP | 8-month-old MLD mice | >90% neurons, 21.4% ± 1.1 oligodendrocytes in the corpus callosum and the internal capsules. | Piguet et al., 2012 |
| AAV9EU-CBA-mCherry AAV9AU-CBA-mCherry |
IC | Sprague-Dawley rats | Neurons (14.2% ± 3.6), oligodendrocytes (79.9% ± 4.6) for AAV9EU-CBA-mCherry. Neurons (89.8 ± 3.9%), oligodendrocytes (2.1 ± 0.8%) for AAV9AU-CBA-mCherry |
Powell et al., 2020 | |
| Olig001-CBh-GFP | Mixed glial cultures from p3 C57BL/6J pups. | 9-fold higher transduction efficiency in glial cells with respect to AAV8. | Powell et al., 2016 | ||
| IS | Adult female C57Bl/6 mice. | >95 striatal oligodendrocytes. | |||
| LV.CNP.IRES.EGFP | ICV, IP | Neonatal C57BL/6 mice | 20.3 ± 2.56% of oligodendrocytes in different CNS regions. | Kagiava et al., 2014 | |
| rAAV5-F4/80-RFP vector | Microglia | Primary rat microglia cultures from p1-p2 pups. | Efficient transgene expression in microglia. | Cucchiarini et al., 2003 | |
| IS | Sprague–Dawley rats. | Selective microglia tropism. | |||
| F4/80-GFP and CD68-GFP expression cassettes in AAV6-TM6 (Y731F/Y705F/T492V mutated capsid) | Primary neuroglia and microglia cultures from neonatal mice. | >95% transduction of primary microglial cells. | Rosario et al., 2016 | ||
| ICV, IP | Neonatal (ICV) and 2-month-old (IP) B6/C3H mice. | Selective microglia tropism. | |||
| rAAV2/6-based recombinant genomes-CMV-eGFP/RFP | Mixed neonatal cortical glia cultures from p3-p4 and adult C57/BL6 mice. | 98 and 99% of RFP+ cells in newborn and adult microglia (rAAV2-CMV-eGFP). 80-fold higher transgene expression (rAAV6-CMV-eGFP). |
Su et al., 2016 | ||
| LV.PGK.GFP LV.PGK.GFP.miR 9.T |
IS | Sprague–Dawley rats | 75% of GFP+ microglia (Iba1+) and 1% of GFP+ striatal neurons (DARPP-32+). | Akerblom et al., 2013 | |
| LV.CMV.Twitch-2B.miR 9.T | IP | 2/6-month-old C57BL/6 mice | 36.58% of transduced microglia (Iba1+). | Brawek et al., 2017 | |
| rAAV1-CMV-IE-GFP | Microglia, Astrocytes, Oligodendrocytes | IS | Adult C3H/HeJ mice | Astrocytes (751 ± 122 cells), oligodendrocytes (164 ± 24 cells), and microglia (101 ± 35 cells). | Wang et al., 2003 |
In the table are reported in vitro and in vivo data on AAV and LV transduction efficiencies in glial cells. IS, Intrastriatal injection; ICV, Intracerebroventricular injection; IP, Intraparenchymal injection; IC, Intracranical injection; IV, Intravenous injection; EC, External Capsule injection; gfaABC1D, minimal GFAP promoter; CBA, chimeric CMV–chicken ß–actin promoter; RSV, Rous Sarcoma Virus Long Terminal Repeat promoter; CMV, Cytomegalovirus promoter; CAG, composite of the CMV early enhancer and chicken beta-actin promoter; CBh, 800-bp hybrid form of the CBA promoter; F4/80 and CD68, microglia-specific promoters; PGK, Phosphoglycerate Kinase promoter.