Work

381. The Adenoviral Fiber Shaft Is a Major Determinant of Kupffer Cell Necrosis

Year: 2006

Type: article

Abstract: When adenoviral vectors are administered systemically, they are quickly taken up by phagocytes of the reticuloendothelial system, including Kupffer cells (KCs) in the liver. We have recently shown in mice that E1/E3_deleted Ad5 vectors cause rapid KC death, followed by a slower depletion of KCs from the liver (Mol. Ther. 13:108_117, 2006). KCs lost membrane integrity within 10 min after i.v. injection of Ad5 vectors, and this eventually resulted in significant depletion of KCs from the liver. In the current study, we investigated which features of the adenoviral fiber contribute to KC toxicity by administering Ad5 vectors with the fiber partially or completely replaced by the type 35 fiber.

Source: Molecular Therapy

DOI: 10.1016/j.ymthe.2006.08.441

Authors: Jeffrey S. Smith, Jie Tian, Susan C. Stevenson, Andrew P. Byrnes

Institutions: Center for Biologics Evaluation and Research, United States Food and Drug Administration

Language: English

Topic: Virus-based gene therapy research

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,500