Intravitreal injection of an exosome-associated adeno-associated viral vector enhances retinoschisin 1 gene transduction in the mouse retina

2021 ◽  
Author(s):  
Weiping Wang ◽  
Jingyang Liu ◽  
Mingzhu Yang ◽  
Ruiqi Qiu ◽  
Ya Li ◽  
...  
Keyword(s):  
Intravitreal Injection ◽  
Viral Vector ◽  
Mouse Retina ◽  
Gene Transduction

scholarly journals Disrupting the LINC complex by AAV mediated gene transduction prevents progression of Lamin induced cardiomyopathy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ruth Jinfen Chai ◽  
Hendrikje Werner ◽  
Peter Yiqing Li ◽  
Yin Loon Lee ◽  
Khaing Thet Nyein ◽  
...  
Keyword(s):  
Cardiac Failure ◽  
Viral Vector ◽  
Nuclear Periphery ◽  
Dominant Negative ◽  
Gene Transduction ◽  
Linc Complex ◽  
Specific Expression ◽  
Common Cause ◽  
Complex Protein ◽  
One Year

AbstractMutations in the LaminA gene are a common cause of monogenic dilated cardiomyopathy. Here we show that mice with a cardiomyocyte-specific Lmna deletion develop cardiac failure and die within 3–4 weeks after inducing the mutation. When the same Lmna mutations are induced in mice genetically deficient in the LINC complex protein SUN1, life is extended to more than one year. Disruption of SUN1’s function is also accomplished by transducing and expressing a dominant-negative SUN1 miniprotein in Lmna deficient cardiomyocytes, using the cardiotrophic Adeno Associated Viral Vector 9. The SUN1 miniprotein disrupts binding between the endogenous LINC complex SUN and KASH domains, displacing the cardiomyocyte KASH complexes from the nuclear periphery, resulting in at least a fivefold extension in lifespan. Cardiomyocyte-specific expression of the SUN1 miniprotein prevents cardiomyopathy progression, potentially avoiding the necessity of developing a specific therapeutic tailored to treating each different LMNA cardiomyopathy-inducing mutation of which there are more than 450.

scholarly journals Adeno-Associated Viral Vector 2 and 9 Transduction Is Enhanced in Streptozotocin-Induced Diabetic Mouse Retina

2019 ◽  
Vol 13 ◽  
pp. 55-66
Author(s):  
Si Hyung Lee ◽  
Jin Young Yang ◽  
Sanjar Madrakhimov ◽  
Ha Yan Park ◽  
Keerang Park ◽  
...  
Keyword(s):  
Viral Vector ◽  
Diabetic Mouse ◽  
Mouse Retina

scholarly journals Transduction of the inner mouse retina using AAVrh8 and AAVrh10 via intravitreal injection

2010 ◽  
Vol 91 (5) ◽  
pp. 652-659 ◽  
Author(s):  
Thomas J. Giove ◽  
Miguel Sena-Esteves ◽  
William D. Eldred
Keyword(s):  
Intravitreal Injection ◽  
Mouse Retina

scholarly journals Co-Injection of Sulfotyrosine Facilitates Retinal Uptake of Hyaluronic Acid Nanospheres Following Intravitreal Injection

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1510
Author(s):  
Aiden Eblimit ◽  
Mustafa S. Makia ◽  
Daniel Strayve ◽  
Ryan Crane ◽  
Shannon M. Conley ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Retinal Pigment Epithelium ◽  
Intravitreal Injection ◽  
Targeted Delivery ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Mouse Retina ◽  
Loss Of Function ◽  
Outer Retina ◽  
Fluorescent Reporters

Gene and drug delivery to the retina is a critical therapeutic goal. While the majority of inherited forms of retinal degeneration affect the outer retina, specifically the photoreceptors and retinal pigment epithelium, effective targeted delivery to this region requires invasive subretinal delivery. Our goal in this work was to evaluate two innovative approaches for increasing both the persistence of delivered nanospheres and their penetration into the outer retina while using the much less invasive intravitreal delivery method. We formulated novel hyaluronic acid nanospheres (HA-NS, 250 nm and 500 nm in diameter) conjugated to fluorescent reporters and delivered them intravitreally to the adult Balb/C mouse retina. They exhibited persistence in the vitreous and along the inner limiting membrane (ILM) for up to 30 days (longest timepoint examined) but little retinal penetration. We thus evaluated the ability of the small molecule, sulfotyrosine, to disrupt the ILM, and found that 3.2 µg/µL sulfotyrosine led to significant improvement in delivery to the outer retina following intravitreal injections without causing retinal inflammation, degeneration, or loss of function. Co-delivery of sulfotyrosine and HA-NS led to robust improvements in penetration of HA-NS into the retina and accumulation along the interface between the photoreceptors and the retinal pigment epithelium. These exciting findings suggest that sulfotyrosine and HA-NS may be an effective strategy for outer retinal targeting after intravitreal injection.

scholarly journals Cellular tropism and transduction properties of seven adeno-associated viral vector serotypes in adult retina after intravitreal injection

Gene Therapy ◽  
2008 ◽  
Vol 16 (4) ◽  
pp. 521-532 ◽  
Author(s):  
M Hellström ◽  
M J Ruitenberg ◽  
M A Pollett ◽  
E M E Ehlert ◽  
J Twisk ◽  
...  
Keyword(s):  
Intravitreal Injection ◽  
Viral Vector ◽  
Adult Retina ◽  
Cellular Tropism

Adeno-associated viral vector-mediated gene transduction in mesencephalic slice culture

2011 ◽  
Vol 201 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Tomoko Nihira ◽  
Toru Yasuda ◽  
Yukihiko Hirai ◽  
Takashi Shimada ◽  
Yoshikuni Mizuno ◽  
...  
Keyword(s):  
Viral Vector ◽  
Slice Culture ◽  
Gene Transduction

scholarly journals Laser Photocoagulation Enhances Adeno-Associated Viral Vector Transduction of Mouse Retina

2014 ◽  
Vol 25 (1) ◽  
pp. 83-91 ◽  
Author(s):  
Si Hyung Lee ◽  
Peter Colosi ◽  
Heuiran Lee ◽  
Young-Hoon Ohn ◽  
Sung-Woon Kim ◽  
...  
Keyword(s):  
Laser Photocoagulation ◽  
Viral Vector ◽  
Mouse Retina ◽  
Vector Transduction
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