Surface Modification of Retroviral Vectors for Gene Therapy

Metzner, Christoph; Dangerfield, John A.

doi:10.5772/20568

Cited by 4 publications

(5 citation statements)

References 149 publications

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“…In this study, we could demonstrate that modification of retroviral vector particles with a regulator of the complement system using MP leaves them less susceptible to complement attack. On a more general note, this provides further evidence for the usefulness of MP in a range of biomedical applications, from labelling of virus particles for research purposes [ 26 ] and vaccination strategies using VLPs [ 32 , 34 ] to fine-tuning vector properties for gene therapy applications [ 25 , 27 , 28 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Immune Protection of Retroviral Vectors Upon Molecular Painting with the Complement Regulatory Protein CD59

et al. 2016

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Glycosylphosphatidylinositol anchoring is a type of post-translational modification that allows proteins to be presented on the exterior side of the cell membrane. Purified glycosylphosphatidylinositol-anchored protein can spontaneously re-insert into lipid bilayer membranes in a process termed Molecular Painting. Here, we demonstrate the possibility of inserting purified, recombinant CD59 into virus particles produced from a murine retroviral producer cell line. CD59 is a regulator of the complement system that helps protect healthy cells from the lytic activity of the complement cascade. In this study, we could show that Molecular Painting confers protection from complement activity upon murine retroviral vector particles. Indeed, increased infectivity of CD59-modified virus particles was observed upon challenge with human serum, indicating that Molecular Painting is suitable for modulating the immune system in gene therapy or vaccination applications.Electronic supplementary materialThe online version of this article (doi:10.1007/s12033-016-9944-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Immune Protection of Retroviral Vectors Upon Molecular Painting with the Complement Regulatory Protein CD59

et al. 2016

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“…The most often used method is pseudotyping with proteins of heterologous viral origin [1, 35] or the use of fusion proteins consisting of mixed viral/nonviral sequences [1, 36, 37]. These require the activity of the cellular expression machinery [1]. In contrast, postexit procedures fall roughly into three categories: (i) direct covalent modification, (ii) the use of membrane-topic moieties, and (iii) the use of adaptor systems (see Figure 1 and Table 1 for an overview).…”

Section: Methodology: How Can R/lv Surfaces Be Modified After Theimentioning

confidence: 99%

“…While this inherent biocompatibility is at least partially responsible for their success, nevertheless a more controlled environment at the surface of R/LV particles would be beneficial for both, simplifying the regulatory/manufacturing aspects of gene therapy approaches as well as enhancing efficacy and safety of such approaches. More specifically, possibilities may be found in several areas: (i) easy concentration and purification of vector stocks for clinical use, (ii) being able to monitor administration and distribution of vectors (both of which can be achieved by suitable labeling), (iii) navigating the host response, especially a patient's immune response, and (iv) targeting of vectors to specific organs, tissues, or cell types (for a more extensive discussion see [1] and see also Figure 1 for an overview). …”

Section: Introduction: Why Modify Retroviral Surfaces?mentioning

confidence: 99%

PostexitSurface Engineering of Retroviral/Lentiviral Vectors

Metzner

Kochan

Dangerfield³

2013

BioMed Research International

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Gene delivery vectors based on retroviral or lentiviral particles are considered powerful tools for biomedicine and biotechnology applications. Such vectors require modification at the genomic level in the form of rearrangements to allow introduction of desired genes and regulatory elements (genotypic modification) as well as engineering of the physical virus particle (phenotypic modification) in order to mediate efficient and safe delivery of the genetic information to the target cell nucleus. Phenotypic modifications are typically introduced at the genomic level through genetic manipulation of the virus producing cells. However, this paper focuses on methods which allow modification of viral particle surfaces after they have exited the cell, that is, directly on the viral particles in suspension. These methods fall into three categories: (i) direct covalent chemical modification, (ii) membrane-topic reagents, and (iii) adaptor systems. Current applications of such techniques will be introduced and their advantages and disadvantages will be discussed.

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“…Also, two independent GPI-APs (CD59 and GFP) could be associated with a lentiviral vector simultaneously ( 18 ). While these approaches were mostly targeted at facilitating gene therapy using VVs ( 18 , 29 , 55 , 89 , 90 ), recently strategies for the use in vaccination were suggested ( 19 , 36 , 51 , 91 , 92 ). In these studies, influenza VLPs were generated in a recombinant baculovirus system ( 93 , 94 ) and modified, on one hand, with either GPI-anchored IL12, GM-CSF, or ICAM-1 (collectively termed GPI immunostimulatory molecules) as adjuvant agents in anti-viral immune responses ( 19 ) and, on the other hand, with GPI-HER2 as a model for protein transfer of a tumor-associated antigen for tumor vaccination ( 36 ).…”

Section: Modification Of Virus Particlesmentioning

confidence: 99%

Biomedical applications of glycosylphosphatidylinositol-anchored proteins

Heider

Dangerfield²,

Metzner

2016

Journal of Lipid Research

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Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) use a unique posttranslational modification to link proteins to lipid bilayer membranes. The anchoring structure consists of both a lipid and carbohydrate portion and is highly conserved in eukaryotic organisms regarding its basic characteristics, yet highly variable in its molecular details. The strong membrane targeting property has made the anchors an interesting tool for biotechnological modification of lipid membrane-covered entities from cells through extracellular vesicles to enveloped virus particles. In this review, we will take a closer look at the mechanisms and fields of application for GPI-APs in lipid bilayer membrane engineering and discuss their advantages and disadvantages for biomedicine.

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Surface Modification of Retroviral Vectors for Gene Therapy

Cited by 4 publications

References 149 publications

Immune Protection of Retroviral Vectors Upon Molecular Painting with the Complement Regulatory Protein CD59

Immune Protection of Retroviral Vectors Upon Molecular Painting with the Complement Regulatory Protein CD59

PostexitSurface Engineering of Retroviral/Lentiviral Vectors

Biomedical applications of glycosylphosphatidylinositol-anchored proteins

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