A Single Intravenous AAV9 Injection Mediates Bilateral Gene Transfer to the Adult Mouse Retina
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{"title"=>"A Single Intravenous AAV9 Injection Mediates Bilateral Gene Transfer to the Adult Mouse Retina", "type"=>"journal", "authors"=>[{"first_name"=>"Alexis Pierre", "last_name"=>"Bemelmans", "scopus_author_id"=>"6508250081"}, {"first_name"=>"Sandra", "last_name"=>"Duqué", "scopus_author_id"=>"20734232300"}, {"first_name"=>"Christel", "last_name"=>"Rivière", "scopus_author_id"=>"9235815500"}, {"first_name"=>"Stéphanie", "last_name"=>"Astord", "scopus_author_id"=>"36835656800"}, {"first_name"=>"Mélissa", "last_name"=>"Desrosiers", "scopus_author_id"=>"55650804800"}, {"first_name"=>"Thibault", "last_name"=>"Marais", "scopus_author_id"=>"8608198800"}, {"first_name"=>"José Alain", "last_name"=>"Sahel", "scopus_author_id"=>"7101991490"}, {"first_name"=>"Thomas", "last_name"=>"Voit", "scopus_author_id"=>"55669992000"}, {"first_name"=>"Martine", "last_name"=>"Barkats", "scopus_author_id"=>"6602235971"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"368726451", "doi"=>"10.1371/journal.pone.0061618", "pmid"=>"23613884", "issn"=>"19326203", "scopus"=>"2-s2.0-84876180986", "sgr"=>"84876180986"}, "id"=>"9091e263-9e66-3a15-98c6-03f3d0b7b5ad", "abstract"=>"Widespread gene delivery to the retina is an important challenge for the treatment of retinal diseases, such as retinal dystrophies. We and others have recently shown that the intravenous injection of a self-complementary (sc) AAV9 vector can direct efficient cell transduction in the central nervous system, in both neonatal and adult animals. We show here that the intravenous injection of scAAV9 encoding green fluorescent protein (GFP) resulted in gene transfer to all layers of the retina in adult mice, despite the presence of a mature blood-eye barrier. Cell morphology studies and double-labeling with retinal cell-specific markers showed that GFP was expressed in retinal pigment epithelium cells, photoreceptors, bipolar cells, Müller cells and retinal ganglion cells. The cells on the inner side of the retina, including retinal ganglion cells in particular, were transduced with the highest efficiency. Quantification of the cell population co-expressing GFP and Brn-3a showed that 45% of the retinal ganglion cells were efficiently transduced after intravenous scAAV9-GFP injection in adult mice. This study provides the first demonstration that a single intravenous scAAV9 injection can deliver transgenes to the retinas of both eyes in adult mice, suggesting that this vector serotype is able to cross mature blood-eye barriers. This intravascular gene transfer approach, by eliminating the potential invasiveness of ocular surgery, could constitute an alternative when fragility of the retina precludes subretinal or intravitreal injections of viral vectors, opening up new possibilities for gene therapy for retinal diseases.", "link"=>"http://www.mendeley.com/research/single-intravenous-aav9-injection-mediates-bilateral-gene-transfer-adult-mouse-retina", "reader_count"=>16, "reader_count_by_academic_status"=>{"Researcher"=>5, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>5, "Other"=>2, "Student > Master"=>2}, "reader_count_by_user_role"=>{"Researcher"=>5, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>5, "Other"=>2, "Student > Master"=>2}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>11, "Medicine and Dentistry"=>2, "Neuroscience"=>1, "Design"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>11}}, "reader_count_by_country"=>{"Netherlands"=>1, "United States"=>1, "Germany"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1024175"], "description"=>"<p>Representative cross sections of the optic nerve (A) and the ciliary body (B) treated for GFP immunofluorescence (green) and stained with DAPI (blue), four weeks after the injection of 2×10<sup>12</sup> vg of scAAV9-GFP into the tail veins of eight-week-old mice. In (A), the boundaries of the retinal nerve fiber layer (originating from the RGC) are clearly demarcated by their pattern of GFP expression (arrowheads) (arrows: GFP-positive axons in the optic nerve). (B) High magnification of the ciliary body, showing strong GFP expression in the epithelial cells. ON: optic nerve; RET: retina; TM: trabecular meshwork. Scale bar: 100 µm.</p>", "links"=>[], "tags"=>["biotechnology", "Genetic engineering", "genetics", "Human genetics", "Gene therapy", "Model organisms", "Animal models", "mouse", "Molecular cell biology", "gene expression", "neuroscience", "Sensory systems", "Visual system", "ophthalmology", "Retinal disorders", "optic", "ciliary", "intravenous", "scaav9-gfp", "injected"], "article_id"=>682208, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Alexis-Pierre Bemelmans", "Sandra Duqué", "Christel Rivière", "Stéphanie Astord", "Mélissa Desrosiers", "Thibault Marais", "José-Alain Sahel", "Thomas Voit", "Martine Barkats"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0061618.g002", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GFP_expression_in_the_optic_nerve_and_the_ciliary_body_of_intravenous_scAAV9_GFP_injected_adult_mice_/682208", "title"=>"GFP expression in the optic nerve and the ciliary body of intravenous scAAV9-GFP injected adult mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-15 00:36:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1024184"], "description"=>"<p>GFP expression in representative cross-sections of the retina of adult mice one month after systemic administration of 2.10<sup>12</sup> vg scAAV-GFP of serotype 9 (A–F) or serotype 2 (G–L) in adult mice (n = 3 per condition). GFP expression was detected in the neural retina in all mice from the serotype 9 treated-group (panel A to F are from three different animals). As expected, the highest transduction efficiency was observed at the level of the RGC layer. In contrast, no GFP expression was detected in the retina after AAV serotype 2 injection (panels G to L are from three different animals). Left panels: GFP immunofluorescence; right panels: merged view of GFP (green) and dapi (blue). ONL: outer nuclear layer; INL: inner nuclear layer; RGC: retinal ganglion cell layer. Scale bar: 100 µm.</p>", "links"=>[], "tags"=>["biotechnology", "Genetic engineering", "genetics", "Human genetics", "Gene therapy", "Model organisms", "Animal models", "mouse", "Molecular cell biology", "gene expression", "neuroscience", "Sensory systems", "Visual system", "ophthalmology", "Retinal disorders", "injection", "aav", "serotype", "transduction", "neural"], "article_id"=>682223, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Alexis-Pierre Bemelmans", "Sandra Duqué", "Christel Rivière", "Stéphanie Astord", "Mélissa Desrosiers", "Thibault Marais", "José-Alain Sahel", "Thomas Voit", "Martine Barkats"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0061618.g003", "stats"=>{"downloads"=>0, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Systemic_injection_of_AAV_serotype_2_does_not_lead_to_transduction_of_the_neural_retina_/682223", "title"=>"Systemic injection of AAV serotype 2 does not lead to transduction of the neural retina.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-15 00:37:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/1024187"], "description"=>"<p>Representative retina sections from adult mice treated for double-immunofluorescence analysis four weeks after the injection of 2×10<sup>12</sup> vg of scAAV9-GFP vectors into the tail vein. (A–C) Double-labeling of transduced RGCs for GFP (green) and Brn-3a (red) (arrowheads indicate double-labeled RGCs and arrows indicate cells expressing GFP only). A transduced photoreceptor is highlighted with an asterisk. (D–F) Double-labeling of bipolar cells for GFP (green) and Chx10 (red). The arrow indicates a Chx10-positive bipolar cell with high levels of GFP. The retinal nerve fiber layer (RNFL), labeled for GFP due to the transduction of upstream RGC, is indicated by an asterisk. No RGC can be seen on this panel which illustrates the central part of the retina (as demonstrated by the thickness of the RNFL). ONL: outer nuclear layer; INL: inner nuclear layer; RGC: retinal ganglion cell layer. Scale bar: 50 µm.</p>", "links"=>[], "tags"=>["biotechnology", "Genetic engineering", "genetics", "Human genetics", "Gene therapy", "Model organisms", "Animal models", "mouse", "Molecular cell biology", "gene expression", "neuroscience", "Sensory systems", "Visual system", "ophthalmology", "Retinal disorders", "rgc", "bipolar"], "article_id"=>682226, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Alexis-Pierre Bemelmans", "Sandra Duqué", "Christel Rivière", "Stéphanie Astord", "Mélissa Desrosiers", "Thibault Marais", "José-Alain Sahel", "Thomas Voit", "Martine Barkats"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0061618.g004", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GFP_expression_in_RGC_and_bipolar_cells_/682226", "title"=>"GFP expression in RGC and bipolar cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-15 00:37:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/1024169"], "description"=>"<p>Retinal cross sections were treated for GFP immunofluorescence (green) and counterstained with DAPI (blue), four weeks after the injection of 2×10<sup>12</sup> vg of scAAV9-GFP into the tail veins of eight-week-old mice. GFP was detected in all retina layers (A–D) and in the ciliary bodies (CB in A). Transduction efficiency was particularly high in the RGC layer (B–C) but GFP was also expressed in the various cell types of the inner nuclear layer (INL), including cells with the morphology of bipolar cells (arrowheads in C) and of Müller cells (arrows in D). Rare GFP-positive photoreceptors (asterisks in B and D) and RPE cells (arrowheads in D and F) were also detected. (E–G) High magnification of GFP-positive (E) Müller cells, (F) RPE cells and (G) photoreceptors. RPE: retinal pigment epithelium; ONL: outer nuclear layer; INL: inner nuclear layer; RGC: retinal ganglion cell layer. Scale bar: 200 µm in A and B; 70 µm in C; 50 µm in D; 20 µm in E–G. A, B and E–G are epifluorescence images; C and D are confocal images.</p>", "links"=>[], "tags"=>["biotechnology", "Genetic engineering", "genetics", "Human genetics", "Gene therapy", "Model organisms", "Animal models", "mouse", "Molecular cell biology", "gene expression", "neuroscience", "Sensory systems", "Visual system", "ophthalmology", "Retinal disorders", "retina", "intravenous", "scaav9-gfp"], "article_id"=>682207, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Alexis-Pierre Bemelmans", "Sandra Duqué", "Christel Rivière", "Stéphanie Astord", "Mélissa Desrosiers", "Thibault Marais", "José-Alain Sahel", "Thomas Voit", "Martine Barkats"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0061618.g001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GFP_expression_in_the_retina_after_the_intravenous_delivery_of_scAAV9_GFP_in_adult_mice_/682207", "title"=>"GFP expression in the retina after the intravenous delivery of scAAV9-GFP in adult mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-15 00:36:47"}

PMC Usage Stats | Further Information

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Relative Metric

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