346. Characterization of Adeno-Associated Virus Sequences in Human Tissues

ABSTRACT The potential for using Adeno-associated virus (AAV) as a vector for human gene therapy has stimulated interest in the Dependovirus genus. Serologic data suggest that AAV infections are prevalent in humans, although analyses of viruses and viral sequences from clinical samples are extremely limited. Molecular techniques were used in this study to successfully detect endogenous AAV sequences in 18% of all human tissues screened, with the liver and bone marrow being the most predominant sites. Sequence characterization of rescued AAV DNAs indicated a diverse array of molecular forms which segregate into clades whose members share functional and serologic similarities. One of the most predominant human clades is a hybrid of two previously described AAV serotypes, while another clade was found in humans and several species of nonhuman primates, suggesting a cross-species transmission of this virus. These data provide important information regarding the biology of parvoviruses in humans and their use as gene therapy vectors.

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Characterization of the lipid droplet-associated protein MLDP in human tissues and in hepatocyte steatosis

Zeitschrift für Gastroenterologie ◽

10.1055/s-0029-1246408 ◽

2010 ◽

Vol 48 (01) ◽

Author(s):

M Hashani ◽

M koenig ◽

LM Pawella ◽

P Schirmacher ◽

BK Straub

Keyword(s):

Lipid Droplet ◽

Human Tissues ◽

Hepatocyte Steatosis

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Characterization of the role of adenovirus-5 (Ad-5) gene products E2A, E4ORF6 and VA RNA on adeno-associated virus type 5 (AAV5) transcription, translation and replication

10.32469/10355/6005 ◽

2007 ◽

Author(s):

Ramnath Nayak

Keyword(s):

Virus Type ◽

Gene Products ◽

Adeno Associated Virus ◽

Adenovirus 5

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The immunological characterization of several human ribonucleases by using primary binding tests

Biochemical Journal ◽

10.1042/bj1630419 ◽

1977 ◽

Vol 163 (3) ◽

pp. 419-426 ◽

Cited By ~ 18

Author(s):

E A Neuwelt ◽

M Schmukler ◽

M S Niziak ◽

P B Jewett ◽

C C Levy

Keyword(s):

Human Plasma ◽

Cross Reaction ◽

The Other ◽

Human Pancreas ◽

Human Tissues ◽

Antigenic Difference ◽

Immunological Characterization ◽

Similarities And Differences

RNAases (ribonucleases), purified from four human tissues, as well as bovine pancreatic RNAase (RNAase A), were studied by immunodiffusion methods and by two different primary binding tests. The enzymes fell into two groups immunologically, those purified from plasma and pancreas in one and those from spleen and liver in the other. No antigenic cross-reaction between the two groups was detected by any of the immunoassays used. There was a slight antigenic cross-reaction between the human and bovine pancreatic RNAases. The liver and spleen RNAases were immunologically identical by all criteria used, whereas a small but consistent antigenic difference between the human plasma and human pancreas enzymes was detected. The significance of this difference between the human plasma and pancreas RNAases is discussed in relation to similarities and differences in their properties.

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744. Genetic Structure of Adeno-Associated Virus DNA in Human Tissues

Molecular Therapy ◽

10.1016/j.ymthe.2004.06.664 ◽

2004 ◽

Vol 9 ◽

pp. S283

Keyword(s):

Genetic Structure ◽

Human Tissues ◽

Adeno Associated Virus

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Isolation and Characterization of Mesoangioblasts from Mouse, Dog, and Human Tissues

Current Protocols in Stem Cell Biology ◽

10.1002/9780470151808.sc02b01s3 ◽

2007 ◽

Vol 3 (1) ◽

Cited By ~ 56

Author(s):

Rossana Tonlorenzi ◽

Arianna Dellavalle ◽

Esther Schnapp ◽

Giulio Cossu ◽

Maurilio Sampaolesi

Keyword(s):

Human Tissues ◽

Isolation And Characterization

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Enhancement of Adeno-Associated Virus-Mediated Gene Therapy Using Hydroxychloroquine in Murine and Human Tissues

Molecular Therapy — Methods & Clinical Development ◽

10.1016/j.omtm.2019.05.012 ◽

2019 ◽

Vol 14 ◽

pp. 77-89 ◽

Cited By ~ 6

Author(s):

Laurel C. Chandler ◽

Alun R. Barnard ◽

Sarah L. Caddy ◽

Maria I. Patrício ◽

Michelle E. McClements ◽

...

Keyword(s):

Gene Therapy ◽

Human Tissues ◽

Adeno Associated Virus

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Characterization of Tissue Tropism Determinants of Adeno-Associated Virus Type 1

Journal of Virology ◽

10.1128/jvi.77.4.2768-2774.2003 ◽

2003 ◽

Vol 77 (4) ◽

pp. 2768-2774 ◽

Cited By ~ 81

Author(s):

Bernd Hauck ◽

Weidong Xiao

Keyword(s):

Amino Acids ◽

Transduction Efficiency ◽

Antigenic Determinants ◽

Tissue Tropism ◽

Heparin Binding ◽

Adeno Associated Virus ◽

Heparin Binding Domain

ABSTRACT Muscle is an attractive target for gene delivery because of its mass and because vectors can be delivered in a noninvasive fashion. Adeno-associated virus (AAV) has been shown to be effective for muscle-targeted gene transfer. Recent progress in characterization of AAV serotype 1 (AAV1) and AAV6 demonstrated that these two AAV serotypes are far more efficient in transducing muscle than is the traditionally used AAV2. Since all cis elements are identical in these vectors, the potential determinants for their differences in transducing muscle appear to be located within the AAV capsid proteins. In the present study, a series of AAV capsid mutants were generated to identify the major regions affecting AAV transduction efficiency in muscle. Replacement of amino acids 350 to 736 of AAV2 VP1 with the corresponding amino acids from VP1 of AAV1 resulted in a hybrid vector that behaved very similarly to AAV1 in vitro and in vivo in muscle. Characterization of additional mutants carrying smaller regions of the AAV1 VP1 amino acid sequence in the AAV2 capsid protein suggested that amino acids 350 to 430 of VP1 function as a major tissue tropism determinant. Further analysis showed that the heparin binding domain and the major antigenic determinants in the AAV capsid region were not necessary for the efficiency of AAV1 transduction of muscle.

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