Antiapoptotic Effect of Gene Therapy with Recombinant Adenovirus Vector Containing Hypoxia-inducible Factor-1α after Cerebral Ischemia and Reperfusion in Rats

This study aimed to investigate the efficacy of gene therapy for treating autoimmune sensorineural hearing loss (ASHL) via local administration of a recombinant adenovirus vector containing the Fas ligand or interleukin IL-10 gene. Guinea pigs were divided into four groups, with different microinjections in the scala tympani. Group A were injected with FasL-EGFP, B with IL-10-EGFP, C with EGFP, and D with artificial perilymph. Seven days later, auditory brain-stem response (ABR) was tested, and the temporal bone was stained and observed by light microscopy. The spiral ligament and basement membrane were observed using transmission electron microscopy. FasL and IL-10 expression were examined using immunofluorescence histochemistry. Immunohistochemical analysis showed that the recombinant adenovirus vector in Groups A, B, and C can transfect the stria vascularis, the spiral ligament, the organ of Corti, the spiral ganglion, the region surrounding the small blood vessel in the modiolus, and the cochlear bone wall. Compared with those in Groups C and D, the ABR wave III mean thresholds were significantly lower and the inner ear immunoinflammatory responses in Groups A and B were significantly alleviated. Inhibition of immunoinflammatory response alleviated immunoinflammatory injury and auditory dysfunction. This technique shows potential as a novel therapy for ASHL.

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Protective effect of hypoxia inducible factor-1α gene therapy using recombinant adenovirus in cerebral ischaemia-reperfusion injuries in rats

Pharmaceutical Biology ◽

10.1080/13880209.2020.1762667 ◽

2020 ◽

Vol 58 (1) ◽

pp. 438-446 ◽

Cited By ~ 2

Author(s):

Ya-Qi Li ◽

Zhi-Rong Hui ◽

Tao Tao ◽

Kang-Yu Shao ◽

Zhi Liu ◽

...

Keyword(s):

Gene Therapy ◽

Protective Effect ◽

Cerebral Ischaemia ◽

Recombinant Adenovirus ◽

Hypoxia Inducible Factor ◽

Hypoxia Inducible Factor 1Α ◽

Ischaemia Reperfusion

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Development of a gene therapy for colorectal cancer using a recombinant adenovirus vector expressing an antisense K-ras RNA

Gastroenterology ◽

10.1016/s0016-5085(00)84221-3 ◽

2000 ◽

Vol 118 (4) ◽

pp. A523

Author(s):

Masaru Nakano ◽

Toshifumi Hibi ◽

Teruhiko Yoshida

Keyword(s):

Colorectal Cancer ◽

Gene Therapy ◽

Recombinant Adenovirus ◽

Adenovirus Vector ◽

Recombinant Adenovirus Vector

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The Revolving Door of Adenovirus Cell Entry: Not All Pathways Are Equal

Pharmaceutics ◽

10.3390/pharmaceutics13101585 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1585

Author(s):

Davor Nestić ◽

Ksenija Božinović ◽

Isabela Pehar ◽

Rebecca Wallace ◽

Alan L. Parker ◽

...

Keyword(s):

Gene Therapy ◽

Recombinant Adenovirus ◽

Adenovirus Vector ◽

Functional Expression ◽

Cell Entry ◽

Revolving Door ◽

Cell Binding ◽

Cancer Treatments ◽

Antiviral Responses ◽

Recombinant Adenovirus Vector

Adenoviruses represent exceptional candidates for wide-ranging therapeutic applications, from vectors for gene therapy to oncolytics for cancer treatments. The first ever commercial gene therapy medicine was based on a recombinant adenovirus vector, while most recently, adenoviral vectors have proven critical as vaccine platforms in effectively controlling the global coronavirus pandemic. Here, we discuss factors involved in adenovirus cell binding, entry, and trafficking; how they influence efficiency of adenovirus-based vectors; and how they can be manipulated to enhance efficacy of genetically modified adenoviral variants. We focus particularly on endocytosis and how different adenovirus serotypes employ different endocytic pathways to gain cell entry, and thus, have different intracellular trafficking pathways that subsequently trigger different host antiviral responses. In the context of gene therapy, the final goal of the adenovirus vector is to efficiently deliver therapeutic transgenes into the target cell nucleus, thus allowing its functional expression. Aberrant or inefficient endocytosis can impede this goal, therefore, it should be considered when designing and constructing adenovirus-based vectors.

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