Adeno-Associated Virus-Mediated Gene Therapy in the Mashlool, Atp1a3Mashl/+, Mouse Model of Alternating Hemiplegia of Childhood

2021 ◽  
Vol 32 (7-8) ◽  
pp. 405-419
Author(s):  
Arsen S. Hunanyan ◽  
Boris Kantor ◽  
Ram S. Puranam ◽  
Courtney Elliott ◽  
Angela McCall ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mouse Model ◽  
Adeno Associated Virus ◽  
Alternating Hemiplegia Of Childhood

scholarly journals Dual AAV-mediated gene therapy restores hearing in a DFNB9 mouse model

2019 ◽  
Vol 116 (10) ◽  
pp. 4496-4501 ◽  
Author(s):  
Omar Akil ◽  
Frank Dyka ◽  
Charlotte Calvet ◽  
Alice Emptoz ◽  
Ghizlene Lahlou ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mouse Model ◽  
Autosomal Recessive ◽  
Therapeutic Option ◽  
The Other ◽  
Therapeutic Window ◽  
Congenital Deafness ◽  
Adeno Associated Virus ◽  
Coding Sequence ◽  
Packaging Capacity

Autosomal recessive genetic forms (DFNB) account for most cases of profound congenital deafness. Adeno-associated virus (AAV)-based gene therapy is a promising therapeutic option, but is limited by a potentially short therapeutic window and the constrained packaging capacity of the vector. We focus here on the otoferlin gene underlying DFNB9, one of the most frequent genetic forms of congenital deafness. We adopted a dual AAV approach using two different recombinant vectors, one containing the 5′ and the other the 3′ portions of otoferlin cDNA, which exceed the packaging capacity of the AAV when combined. A single delivery of the vector pair into the mature cochlea ofOtof−/−mutant mice reconstituted the otoferlin cDNA coding sequence through recombination of the 5′ and 3′ cDNAs, leading to the durable restoration of otoferlin expression in transduced cells and a reversal of the deafness phenotype, raising hopes for future gene therapy trials in DFNB9 patients.

scholarly journals AAV-mediated gene therapy produces fertile offspring in the Lhcgr-deficient mouse model of Leydig cell failure

2021 ◽  
Author(s):  
Kai Xia ◽  
Fulin Wang ◽  
Xingqiang Lai ◽  
Peng Luo ◽  
Hong Chen ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mouse Model ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Serum Testosterone ◽  
Deficient Mouse ◽  
Proof Of Concept ◽  
Adeno Associated Virus ◽  
Promising Therapeutic Approach ◽  
Efficient Vector

Leydig cell failure (LCF) caused by gene mutation results in testosterone deficiency and infertility. Serum testosterone levels can be recovered via testosterone replacement; however, established therapies have shown limited success in restoring fertility. Here, we used a luteinizing hormone/choriogonadotrophin receptor (Lhcgr)-deficient mouse model of genetic LCF to investigate the feasibility of gene therapy for restoring testosterone production and fertility. We screened several adeno-associated virus (AAV) serotypes and identified AAV8 as an efficient vector to drive exogenous Lhcgr expression in progenitor Leydig cells through interstitial injection. We observed considerable testosterone recovery and Leydig cell maturation after AAV8-Lhcgr treatment in pubertal Lhcgr-/- mice. This gene therapy substantially recovered sexual development, partially restored spermatogenesis and effectively produced fertile offspring. Furthermore, these favorable effects could be reproduced in adult Lhcgr-/- mice. Our proof-of-concept experiments in this mouse model demonstrate that AAV-mediated gene therapy may represent a promising therapeutic approach for patients with genetic LCF.

scholarly journals Intramuscular E-selectin/adeno-associated virus gene therapy promotes wound healing in an ischemic mouse model

2018 ◽  
Vol 228 ◽  
pp. 68-76 ◽  
Author(s):  
Punam P. Parikh ◽  
Roberta M. Lassance-Soares ◽  
Hongwei Shao ◽  
Manuela M. Regueiro ◽  
Yan Li ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Wound Healing ◽  
Mouse Model ◽  
Adeno Associated Virus ◽  
Virus Gene

scholarly journals Gene therapy for tuberous sclerosis complex type 2 in a mouse model by delivery of AAV9 encoding a condensed form of tuberin

2021 ◽  
Vol 7 (2) ◽  
pp. eabb1703
Author(s):  
Pike-See Cheah ◽  
Shilpa Prabhakar ◽  
David Yellen ◽  
Roberta L. Beauchamp ◽  
Xuan Zhang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mouse Model ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Suppressor Gene ◽  
Brain Pathology ◽  
Adeno Associated Virus ◽  
Condensed Form ◽  
Life Threatening ◽  
Cell Growth And Proliferation

Tuberous sclerosis complex (TSC) results from loss of a tumor suppressor gene - TSC1 or TSC2, encoding hamartin and tuberin, respectively. These proteins formed a complex to inhibit mTORC1-mediated cell growth and proliferation. Loss of either protein leads to overgrowth lesions in many vital organs. Gene therapy was evaluated in a mouse model of TSC2 using an adeno-associated virus (AAV) vector carrying the complementary for a “condensed” form of human tuberin (cTuberin). Functionality of cTuberin was verified in culture. A mouse model of TSC2 was generated by AAV-Cre recombinase disruption of Tsc2-floxed alleles at birth, leading to a shortened lifespan (mean 58 days) and brain pathology consistent with TSC. When these mice were injected intravenously on day 21 with AAV9-cTuberin, the mean survival was extended to 462 days with reduction in brain pathology. This demonstrates the potential of treating life-threatening TSC2 lesions with a single intravenous injection of AAV9-cTuberin.

Total correction of hemophilia A mice with canine FVIII using an AAV 8 serotype

Blood ◽  
2004 ◽  
Vol 103 (4) ◽  
pp. 1253-1260 ◽  
Author(s):  
Rita Sarkar ◽  
Renee Tetreault ◽  
Guangping Gao ◽  
Lili Wang ◽  
Peter Bell ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Mouse Model ◽  
Light Chain ◽  
Hemophilia A ◽  
The Other ◽  
Total Correction ◽  
Adeno Associated Virus ◽  
Vector Type ◽  
Fviii Activity

Abstract Despite the popularity of adeno-associated virus 2 (AAV2) as a vehicle for gene transfer, its efficacy for liver-directed gene therapy in hemophilia A or B has been suboptimal. Here we evaluated AAV serotypes 2, 5, 7, and 8 in gene therapy of factor VIII (FVIII) deficiency in a hemophilia A mouse model and found that AAV8 was superior to the other 3 serotypes. We expressed canine B domain-deleted FVIII cDNA either in a single vector or in 2 separate AAV vectors containing the heavy- and light-chain cDNAs. We also evaluated AAV8 against AAV2 in intraportal and tail vein injections. AAV8 gave 100% correction of plasma FVIII activity irrespective of the vector type or route of administration.

scholarly journals Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model

2004 ◽  
Vol 10 (8) ◽  
pp. 1191 ◽  
Author(s):  
Sung Yi Hong ◽  
Myun Hee Lee ◽  
Kyung Sup Kim ◽  
Hyun Cheol Jung ◽  
Jae Kyung Roh ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mouse Model ◽  
Liver Tumor ◽  
Adeno Associated Virus ◽  
Topoisomerase Inhibitor
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