Herpes Simplex Virus Type 1 Thymidine Kinase Sequence Fused to the
            <i>lacZ</i>
            Gene Increases Levels of β-Galactosidase Activity per Genome of High-Capacity but Not First-Generation Adenoviral Vectors In Vitro and In Vivo

Puntel, Mariana; Barrett, Robert J.; Mondkar, Sonali; Saxena, Vandana; Kroeger, Kurt M.; Muhammad, A.K.M. Ghulam; Liu, C.; Bondale, Niyati; Sciascia, Sandra A.; Xiong, Wei; Shi, Yuan; Salem, Alireza; Zadmehr, Ali; Huynh, Phuong Truc; Palmer, D. Jason; Ng, Philip; Castro, María G.; Löwenstein, Pedro R.

doi:10.1128/jvi.01298-08

Cited by 2 publications

(3 citation statements)

References 54 publications

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“…The WPRE element has been included in gene therapy vectors with the goal of increasing transduction levels. However, the impact of WPRE inclusion on transgene expression is variable and depends on the context of the promoter [43] , [67] – [69] , the transgene [70] , the gene transfer vector used [49] , [54] and target cell type [42] , [68] , [69] , [71] – [73] . Notably, in some instances the use of WPRE has been reported to decrease transgene expression levels [69] , [72] – [75] .…”

Section: Discussionmentioning

confidence: 99%

Impact of Age at Administration, Lysosomal Storage, and Transgene Regulatory Elements on AAV2/8-Mediated Rat Liver Transduction

et al. 2012

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Liver-directed gene transfer is being investigated for the treatment of systemic or liver-specific diseases. Recombinant vectors based on adeno-associated virus serotype 8 (AAV2/8) efficiently transduce liver cells allowing long term transgene expression after a single administration in animal models and in patients. We evaluated the impact on AAV2/8-mediated rat liver transduction of the following variables: i) age at vector administration, ii) presence of lysosomal storage in liver cells, and iii) regulatory elements included in the transgene expression cassette. We found that systemic administration of AAV2/8 to newborn rats results in vector genome dilution and reduced transduction efficacy when compared to adult injected animals, presumably due to hepatocyte proliferation. Accumulation of glycosaminoglycans in lysosomes does not impact on levels and distribution of AAV2/8-mediated liver transduction. Transgene expression occurs in hepatocytes but not in Kupffer or liver endothelial cells when the liver-specific thyroxine-binding-globulin promoter is used. However, extra-hepatic transduction is observed in the spleen and kidney of animals injected at birth. The use of target sequences for the hematopoietic-specific microRNA miR142-3p does not improve liver transduction efficacy neither reduce immune responses to the lysosomal enzyme arylsulfatase B. The inclusion of a variant of the Woodchuck hepatitis virus post-transcriptional regulatory element (WPRE-m) decreases AAV2/8-mediated liver transduction levels. As AAV2/8-mediated liver gene transfer is entering in the clinical arena, these data will provide relevant information to the design of efficient AAV2/8-based therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Impact of Age at Administration, Lysosomal Storage, and Transgene Regulatory Elements on AAV2/8-Mediated Rat Liver Transduction

et al. 2012

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“…In addition, a specific increased transgene expression per vector genome is an important goal for the optimization of viral vectors in immunotherapy. Adenoviral vectors induce dose-dependent innate and adaptive immune responses [17]. Decreasing the total dose of therapeutically effective viral vector should result in safe and long-term gene transfer.…”

Section: Hsv-vector Vaccinesmentioning

confidence: 99%

“…Decreasing the total dose of therapeutically effective viral vector should result in safe and long-term gene transfer. The Lowenstein and Castro group recently demonstrated that HSV-1 TK gene sequences fused to the 3´-end of lacZ increase transgene expression from high-capacity adenoviral vectors [17]. These are the highly desirable prospects for the development of safe, efficacious adenoviral vectors that can be used as an immunotherapeutic approach for human herpes diseases.…”

Section: Hsv-vector Vaccinesmentioning

confidence: 99%

Future Viral Vectors For the Delivery of Asymptomatic Herpes Epitope-based Immunotherapeutic Vaccines

Chentoufi

BenMohamed

2010

Future Virol.

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Herpes Simplex Virus Type 1 Thymidine Kinase Sequence Fused to the lacZ Gene Increases Levels of β-Galactosidase Activity per Genome of High-Capacity but Not First-Generation Adenoviral Vectors In Vitro and In Vivo

Cited by 2 publications

References 54 publications

Impact of Age at Administration, Lysosomal Storage, and Transgene Regulatory Elements on AAV2/8-Mediated Rat Liver Transduction

Impact of Age at Administration, Lysosomal Storage, and Transgene Regulatory Elements on AAV2/8-Mediated Rat Liver Transduction

Future Viral Vectors For the Delivery of Asymptomatic Herpes Epitope-based Immunotherapeutic Vaccines

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