Development of a Pharmaceutical Apotransferrin Product for Iron Binding Therapy

Bonsdorff, Leni von; Tölö, Hannele; Lindeberg, Enni; Nyman, Tuula A.; Harju, Anna; Parkkinen, Jaakko

doi:10.1006/biol.2001.0273

Cited by 40 publications

(34 citation statements)

References 32 publications

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“…AGP-A is a form of AGP that contains a reduced amount of biantennary chains (37a). Apo-transferrin is known to be glycosylated with two biantennary N-linked glycan chains that contain ␣2,6 terminal sialic acids linked to lactosamine (4,38). Fractions of glycans purified from AGP, AGP-A, and apo-transferrin can also be fucosylated to create the sLe X motif [NeuAc␣2-3/6Gal␤1-4(Fuc␣1-3)GlcNAc], which is a marker for cancer cells.…”

Section: Vol 80 2006 Sialic Acid Is Required For Aav1 and Aav6 Tranmentioning

confidence: 99%

α2,3 and α2,6 N-Linked Sialic Acids Facilitate Efficient Binding and Transduction by Adeno-Associated Virus Types 1 and 6

Miller

Agbandje‐McKenna

et al. 2006

J Virol

271

227

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Recombinant adeno-associated viruses (AAVs) are promising vectors in the field of gene therapy. Different AAV serotypes display distinct tissue tropism, believed to be related to the distribution of their receptors on target cells. Of the 11 well-characterized AAV serotypes, heparan sulfate proteoglycan and sialic acid have been suggested to be the attachment receptors for AAV type 2 and types 4 and 5, respectively. In this report, we identify the receptor for the two closely related serotypes, AAV1 and AAV6. First, we demonstrate using coinfection experiments and luciferase reporter analysis that AAV1 and AAV6 compete for similar receptors. Unlike heparin sulfate, enzymatic or genetic removal of sialic acid markedly reduced AAV1 and AAV6 binding and transduction. Further analysis using lectin staining and lectin competition assays identified that AAV1 and AAV6 use either ␣2,3-linked or ␣2,6-linked sialic acid when transducing numerous cell types (HepG2, Pro-5, and Cos-7). Treatment of cells with proteinase K but not glycolipid inhibitor reduced AAV1 and AAV6 infection, supporting the hypothesis that the sialic acid that facilitates infection is associated with glycoproteins rather than glycolipids. In addition, we determined by inhibitor (N-benzyl GalNAc)-and cell line-specific (Lec-1) studies that AAV1 and AAV6 require N-linked and not O-linked sialic acid. Furthermore, a resialylation experiment on a deficient Lec-2 cell line confirmed a 2,3 and 2,6 N-linked sialic acid requirement, while studies of mucin with O-linked sialic acid showed no inhibition effect for AAV1 and AAV6 transduction on Cos-7 cells. Finally, using a glycan array binding assay we determined that AAV1 efficiently binds to NeuAc␣2-3GalNAc␤1-4GlcNAc, as well as two glycoproteins with ␣2,3 and ␣2,6 N-linked sialic acids. Taken together, competition, genetic, inhibitor, enzymatic reconstitution, and glycan array experiments support ␣2,3 and ␣2,6 sialic acids that are present on N-linked glycoproteins as primary receptors for efficient AAV1 and AAV6 viral infection.Adeno-associated viruses (AAVs), dependoviruses of the parvovirus family, rely on a helper virus, such as adenovirus or herpesvirus, to complete their life cycle. In recent years, AAVs have become promising vectors for gene therapy, due to their nonpathogenicity and their ability to mediate long-term transgene expression. Among the 11 AAV serotypes (AAV1 to AAV11) and over 100 variants (12,24), AAV2 is the best characterized and the predominant serotype used in clinical trials. However, more and more studies suggest that AAV2-based vectors are rate limiting in certain tissues (5, 32). The availability of other AAV serotypes with tissue preference for transduction, such as AAV1 and AAV6 for muscle (2, 5) and AAV8 for liver (12,14,25), has overcome this restriction. The enhanced tropism of AAV serotypes in different organs is dictated by their capsid amino acid sequences and is believed in part to be related to the cumulative effects of viral binding to multiple cell surface receptors,...

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Section: Vol 80 2006 Sialic Acid Is Required For Aav1 and Aav6 Tranmentioning

confidence: 99%

α2,3 and α2,6 N-Linked Sialic Acids Facilitate Efficient Binding and Transduction by Adeno-Associated Virus Types 1 and 6

Miller

Agbandje‐McKenna

et al. 2006

J Virol

271

227

View full text Add to dashboard Cite

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“…The procedures were tolerated well and liver function tests improved in 21 (91%) patients. Apotransferrin is an investigational human plasma-derived product used for iron-binding therapy, 105 and has been used in clinical trials in the setting of HSCT with reduction in TS. 106 In this study, it was shown that free iron was bound by the conversion of transferrin into monoferric and diferric forms.…”

Section: Interventionmentioning

confidence: 99%

Rust and corrosion in hematopoietic stem cell transplantation: the problem of iron and oxidative stress

Evens

Mehta

2004

Bone Marrow Transplant

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“…The icosahedral nonenveloped B19 virion is resistant to ordinary physicochemical factors, including solvent-detergent treatment. Because of its minute size, the pathogen is also relatively resistant to filtration (26), although it is in part removable with small-pore-size filters (4,28). By PCR screening it is possible to restrict the DNA load and obtain safe plasma products (28).…”

mentioning

confidence: 99%

Detection and Differentiation of Human Parvovirus Variants by Commercial Quantitative Real-Time PCR Tests

Hokynar¹,

Norja²,

Laitinen

et al. 2004

J Clin Microbiol

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Parvovirus B19 causes a variety of diseases in humans, with outcomes ranging from asymptomatic to severe, such as chronic anemia in immunocompromised patients or fetal hydrops and death after maternal infection during pregnancy. The virus may be transmitted via plasma-derived products. According to the results of solventdetergent safety studies, an upper limit of B19 DNA in plasma pools was recently defined. To restrict the input of B19 virus into production pools, a quantitative nucleic acid test is a prerequisite. We examined the suitability of the two commercial quantitative B19 PCR tests, LightCycler-Parvovirus B19 quantification kit (Roche Diagnostics) and RealArt Parvo B19 LC PCR (Artus) for detection, quantification, and differentiation of the three known B19 genotypes, including the newly described erythrovirus variants (genotypes 2 and 3). The former kit was highly sensitive for genotype 1 but was not suitable for detection of genotype 2 or one of two genotype 3 strains. The latter kit detected and differentiated all three genotypes, albeit with lower sensitivity for one of the genotype-3 strains. We furthermore assessed the prevalence of the three B19 virus genotypes in blood donors, by screening pooled plasma samples derived from 140,160 Finnish blood-donor units. None of the pools contained detectable levels of B19 virus genotypes 2 or 3. The origin, mode of transmission, and clinical significance of these genotypes are unknown and deserve further study. The RealArt Parvo B19 LC PCR is suitable for detection, quantification, and differentiation of all three B19 virus genotypes in molecular and clinical research.

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Development of a Pharmaceutical Apotransferrin Product for Iron Binding Therapy

Cited by 40 publications

References 32 publications

α2,3 and α2,6 N-Linked Sialic Acids Facilitate Efficient Binding and Transduction by Adeno-Associated Virus Types 1 and 6

α2,3 and α2,6 N-Linked Sialic Acids Facilitate Efficient Binding and Transduction by Adeno-Associated Virus Types 1 and 6

Rust and corrosion in hematopoietic stem cell transplantation: the problem of iron and oxidative stress

Detection and Differentiation of Human Parvovirus Variants by Commercial Quantitative Real-Time PCR Tests

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