Cover legend: Cellular tropism of Adeno-Associated Virus vector AAVrh10 in the rat retina. Eyes were injected intravitreally with AAVrh10-CMV-EGFP at a dose of 2.5e12 vector genomes/eye. Retinal sections were counter-stained with GFP and parvalbumin antibodies. GFP-positive cells, transduced by AAVrh10 vector, show green fluorescence. Parvalbumin-positive cells (a subgroup of amacrine and ganglion cells) show red fluorescence. AAVrh10 vector-transduced amacrine and ganglion cells show yellow fluorescence. Cell nuclei were visualized by DAPI staining (blue). See article by Zeng et al in the September 2019 issue of Gene Therapy.

Cover credit: Alfred Pasieka/Science Photo Library

Cover credit: Alfred Pasieka/Science Photo Library

Cover legend: The dorsal root ganglion (DRG) is a particularly accessible site for targeting new analgesic treatments. Small peptides targeting ion channel proteins as functionally inhibitory peptide aptamers are highly effective and selective blockers of specific protein-protein interactions (PPIs) in nociceptive molecular pathways to reduce pain. Their sustained expression in sensory neurons delivered by recombinant adeno-associated virus (AAV) into the DRG is a safe and feasible treatment of chronic pain. This issue of Gene Therapy describes an AAV-encoded CaV2.2 peptide aptamer CBD3A6K targeting primary sensory neurons for treatment of established neuropathic pain. The images show that intraganglionic AAV delivery induces effi cient expression of fluorescent CBD3A6K selectively in the CaV2.2-expressing sensory neurons and transgene transport to the spinal cord dorsal horn. See paper by Yu et al. in this issue of Gene Therapy.

Astrocytes play a critical role in the on-going secondary damage in spinal cord injury, and an adeno-associated viral (AAV) vector that targets astrocytes could show benefit as a potential treatment. Robust, astrocyte-selective transgene expression by AAV vectors in the spinal cord was achieved by utilising a full-length glial fibrillary acidic protein (GFAP), or a truncated GfaABC1D promoter to drive destabilised yellow fluorescent protein (dYFP) transgene expression. The image shows the colocalisation (yellow) of dYFP to GFAP immunofluorescence within astrocytes in the rat spinal cord. See paper by Griffin et al. in this issue of Gene Therapy.

Helper-dependent Adenovirus (HD-Ad) vector-mediated expression of a chimeric low density lipoprotein receptor (LDLR)-transferrin protein reduces aortic atherosclerosis development in a Familial Hypercholesterolemia (FH) mouse model. Gene therapy approaches for FH are of increasing interest since they may represent a definitive or long-lasting cure for patients. HD-Ad vector-mediated expression of a chimeric secreted protein, composed of the extracellular portion of the LDLR and a transferrin dimer, led to significant, long-lasting reduction of aortic atherosclerosis in LDLR-deficient mice, a model of human FH. The image shows Oil-Red-O lipid staining of aortic plaque deposits in treated and untreated LDLR-deficient mice. See paper by Leggiero et al. in this issue of Gene Therapy.

Alfred Pasieka/Science Photo Library