Biomedical applications of glycosylphosphatidylinositol-anchored proteins
2016; Elsevier BV; Volume: 57; Issue: 10 Linguagem: Inglês
10.1194/jlr.r070201
ISSN1539-7262
AutoresSusanne Heider, John A. Dangerfield, Christoph Metzner,
Tópico(s)Cellular transport and secretion
ResumoGlycosylphosphatidylinositol (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. 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. Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are generated by posttranslational modification and can be found on approximately 0.5 percent of proteins in eukaryotes (1Eisenhaber B. Bork P. Eisenhaber F. Post-translational GPI lipid anchor modification of proteins in kingdoms of life: analysis of protein sequence data from complete genomes.Protein Eng. 2001; 14: 17-25Crossref PubMed Scopus (146) Google Scholar), while similar structures are also found in archaea (2Kobayashi T. Nishizaki R. Ikezawa H. The presence of GPI-linked protein(s) in an archaeobacterium, Sulfolobus acidocaldarius, closely related to eukaryotes.Biochim. Biophys. Acta. 1997; 1334: 1-4Crossref PubMed Scopus (40) Google Scholar). While the core structure of the GPI anchor is fairly conserved, i.e., a phosphoethanolamine linker located at the protein C terminus that is coupled to a glycan core mostly consisting of mannose residues, glucosamine, and inositol, which in turn comprise the head-group of the phospholipid (see Fig. 1), fatty acid residues can vary significantly as well as carbohydrate side chains. Proteins are singled out for GPI anchoring due to the presence of a GPI signaling sequence (GSS). The GSS contains the later site of GPI attachment (the amino acid in the ω position) and a series of hydrophobic amino acids, essentially forming a membrane-associating domain linking the pre-GPI protein to the luminal side of the endoplasmic reticulum. Biosynthesis of the anchor occurs separately and consists of a complex series of enzymatic reactions involving more than 11 enzymes (3Ferguson M.A.J. Kinoshita T. Hart G.W. et al.Glycosylphosphatidylinositol anchors.in: Varki A. Cummings R.D. Esko J.D. In Essentials of Glycobiology. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY2009: 143-161Google Scholar). Synthesis starts at the cytosolic side of the endoplasmic reticulum with phosphoinositol, flips to the lumenal side, and sequentially adds the carbohydrate core elements. The transamidase enzyme complex replaces the GSS with the preformed GPI anchor by amide bond formation to the amino acid in the ω position. The GPI-APs are then transported to their final destination via the Golgi system. During transport, further modification of the anchor lipids occurs in a process termed lipid remodeling (4Kinoshita T. Fujita M. Biosynthesis of GPI-anchored proteins: special emphasis on GPI lipid remodeling.J. Lipid Res. 2016; 57: 6-24Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar). GPI-APs may be lost from the membrane either with their anchors intact, in a process termed shedding, or upon enzymatic cleavage, i.e., by phosphoinositol-specific phospholipases B and C (5Sharom F.J. Radeva G. GPI-anchored protein cleavage in the regulation of transmembrane signals.Subcell. Biochem. 2004; 37: 285-315Crossref PubMed Scopus (37) Google Scholar) (see Fig. 1). Biosynthesis, biochemistry and cell biology, trafficking, organization, and dynamics at the cell surface and the release of GPI-APs have all been reviewed recently in greater detail (4Kinoshita T. Fujita M. Biosynthesis of GPI-anchored proteins: special emphasis on GPI lipid remodeling.J. Lipid Res. 2016; 57: 6-24Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar, 6Zurzolo C. Simons K. Glycosylphosphatidylinositol-anchored proteins: membrane organization and transport.Biochim. Biophys. Acta. 2016; 1858: 632-639Crossref PubMed Scopus (84) Google Scholar, 7Kinoshita T. Glycosylphosphatidylinositol (GPI) anchors: biochemistry and cell biology.J. Lipid Res. 2016; 57: 4-5Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, 8Kinoshita T. Structural changes of GPI anchor after its attachment to proteins: functional significance.Adv. Exp. Med. Biol. 2015; 842: 17-25Crossref PubMed Scopus (7) Google Scholar, 9Saha S. Anilkumar A.A. Mayor S. GPI-anchored protein organization and dynamics at the cell surface.J. Lipid Res. 2016; 57: 159-175Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar, 10Muñiz M. Riezman H. Trafficking of glycosylphosphatidylinositol anchored proteins from the endoplasmic reticulum to the cell surface.J. Lipid Res. 2016; 57: 352-360Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar, 11Fujihara Y. Ikawa M. GPI-AP release in cellular, developmental, and reproductive biology.J. Lipid Res. 2016; 57: 538-545Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar). To these detailed insights into the topic, we would like to add information about the applications of GPI-APs in biotechnology, and more specifically, in biomedicine (12Metzner C. Legler D. Dangerfield J.A. Surface engineering of biomembranes with GPI-anchored proteins and its applications.in: Dangerfield J.A. Metzner C. In GPI Membrane Anchors - The Much Needed Link. Bentham Science Publishers, Sharjah, United Arab Emirates2010: 116-137Google Scholar, 13Metzner C. Salmons B. Gunzburg W.H. Dangerfield J.A. Rafts, anchors and viruses - a role for glycosylphosphatidylinositol anchored proteins in the modification of enveloped viruses and viral vectors.Virology. 2008; 382: 125-131Crossref PubMed Scopus (31) Google Scholar, 14Müller G. Novel applications for glycosylphosphatidylinositol-anchored proteins in pharmaceutical and industrial biotechnology.Mol. Membr. Biol. 2011; 28: 187-205Crossref PubMed Scopus (11) Google Scholar). These applications are mainly based on the membrane-targeting properties of GPI-APs and directed at modifying or functionalizing lipid bilayer membranes. This can be achieved in two different ways: by genetic (genotypic) engineering (GE) or by protein engineering [PE, also termed phenotypic engineering, protein transfer, or molecular painting (MP)]. Figure 2 summarizes the differences, advantages, and disadvantages of the two strategies. Hallmarks of the development of GPI-AP membrane engineering are depicted in Fig. 3.Fig. 2Overview of GPI-AP membrane engineering. Two different strategies are employed to modify lipid bilayer membranes with GPI-AP: GE (left) introduces recombinant DNA to express and display the proteins in cell membranes (B) and derived vesicles, such as virus particles (C) and exosomes (A). The vesicles receive GPI-APs as a result of co-incorporation during particle production. In PE (right) purified GPI-APs are inserted directly into the membranes of cells (B), virus envelopes (C), or membrane vesicles, e.g., exosomes (A), from an external source in a process termed, variably, PE, protein transfer, or MP. The advantages and disadvantages are briefly listed at the bottom of the figure. For more details see the Discussion, Summary, and Conclusions section.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig. 3Landmarks in GPI-AP membrane engineering. The timeline depicts a selection of key developments in GPI-AP engineering of cellular (top), viral (middle), and other (bottom) lipid bilayer membranes facilitated by GE (clear bubbles) or PE (gray bubbles). EV, extracellular vesicles; HV, herpesviridae; MV, membrane vesicles; OV, orthomyxoviridae; PT, protein transfer; RV, retroviridae; scFv, single chain variable fragment. References to publications can be found in parentheses. For additional information on the proteins used, see Table 1.View Large Image Figure ViewerDownload Hi-res image Download (PPT) GE introduces recombinant DNA containing the key sorting signals of N-terminal signal peptide and C-terminal GSS into suitable producing cell lines, e.g., via transfection or infection methods (15Kueng H.J. Leb V.M. Haiderer D. Raposo G. Thery C. Derdak S.V. Schmetterer K.G. Neunkirchner A. Sillaber C. Seed B. et al.General strategy for decoration of enveloped viruses with functionally active lipid-modified cytokines.J. Virol. 2007; 81: 8666-8676Crossref PubMed Scopus (32) Google Scholar, 16Zhao F. Dou J. Wang J. Chu L. Tang Q. Wang Y. Li Y. Cao M. Hu W. Hu K. et al.Investigation on the anti-tumor efficacy by expression of GPI-anchored mIL-21 on the surface of B16F10 cells in C57BL/6 mice.Immunobiology. 2010; 215: 89-100Crossref PubMed Scopus (17) Google Scholar, 17Kooijmans S.A. Aleza C.G. Roffler S.R. van Solinge W.W. Vader P. Schiffelers R.M. Display of GPI-anchored anti-EGFR nanobodies on extracellular vesicles promotes tumour cell targeting.J. Extracell. Vesicles. 2016; 5: 31053Crossref PubMed Scopus (228) Google Scholar). GSS elements are commonly derived from the naturally GPI-anchored regulators of the complement system cluster of differentiation (CD)55 (18Metzner C. Kochan F. Dangerfield J.A. Fluorescence molecular painting of enveloped viruses.Mol. Biotechnol. 2013; 53: 9-18Crossref PubMed Scopus (15) Google Scholar), CD59 (19Patel J.M. Kim M.C. Vartabedian V.F. Lee Y.N. He S. Song J.M. Choi H.J. Yamanaka S. Amaram N. Lukacher A. et al.Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses.Nanomedicine. 2015; 11: 1097-1107Crossref PubMed Scopus (19) Google Scholar), or the Fc-receptor CD16b (15Kueng H.J. Leb V.M. Haiderer D. Raposo G. Thery C. Derdak S.V. Schmetterer K.G. Neunkirchner A. Sillaber C. Seed B. et al.General strategy for decoration of enveloped viruses with functionally active lipid-modified cytokines.J. Virol. 2007; 81: 8666-8676Crossref PubMed Scopus (32) Google Scholar). The choice of the GSS can determine the cell membrane compartment localization (20Legler D.F. Doucey M.A. Schneider P. Chapatte L. Bender F.C. Bron C. Differential insertion of GPI-anchored GFPs into lipid rafts of live cells.FASEB J. 2005; 19: 73-75Crossref PubMed Scopus (98) Google Scholar).The recombinant DNA constructs will express, modify, traffic, and finally display recombinant GPI-APs. The natural GPI-anchoring biosynthesis pathway is subverted to display the protein of interest. Generating such GPI-AP-producing cell lines is also a necessary prerequisite for purification of GPI-APs when conducting MP. Extracellular membrane vesicles produced from these cells will contain the recombinant GPI-APs (15Kueng H.J. Leb V.M. Haiderer D. Raposo G. Thery C. Derdak S.V. Schmetterer K.G. Neunkirchner A. Sillaber C. Seed B. et al.General strategy for decoration of enveloped viruses with functionally active lipid-modified cytokines.J. Virol. 2007; 81: 8666-8676Crossref PubMed Scopus (32) Google Scholar, 17Kooijmans S.A. Aleza C.G. Roffler S.R. van Solinge W.W. Vader P. Schiffelers R.M. Display of GPI-anchored anti-EGFR nanobodies on extracellular vesicles promotes tumour cell targeting.J. Extracell. Vesicles. 2016; 5: 31053Crossref PubMed Scopus (228) Google Scholar). When the GPI-producing cells are generating enveloped virus-like particles (VLPs), viruses, or viral vectors (VVs), GPI-APs will be included in the viral envelope (15Kueng H.J. Leb V.M. Haiderer D. Raposo G. Thery C. Derdak S.V. Schmetterer K.G. Neunkirchner A. Sillaber C. Seed B. et al.General strategy for decoration of enveloped viruses with functionally active lipid-modified cytokines.J. Virol. 2007; 81: 8666-8676Crossref PubMed Scopus (32) Google Scholar, 21Skountzou I. Quan F.S. Gangadhara S. Ye L. Vzorov A. Selvaraj P. Jacob J. Compans R.W. Kang S.M. Incorporation of glycosylphosphatidylinositol-anchored granulocyte- macrophage colony-stimulating factor or CD40 ligand enhances immunogenicity of chimeric simian immunodeficiency virus-like particles.J. Virol. 2007; 81: 1083-1094Crossref PubMed Scopus (66) Google Scholar, 22Breun S. Salmons B. Gunzburg W.H. Baumann J.G. Protection of MLV vector particles from human complement.Biochem. Biophys. Res. Commun. 1999; 264: 1-5Crossref PubMed Scopus (12) Google Scholar) as a result of the colocalization of viral exit points and GPI-APs in membrane domains, i.e., lipid rafts (LRs) (13Metzner C. Salmons B. Gunzburg W.H. Dangerfield J.A. Rafts, anchors and viruses - a role for glycosylphosphatidylinositol anchored proteins in the modification of enveloped viruses and viral vectors.Virology. 2008; 382: 125-131Crossref PubMed Scopus (31) Google Scholar, 23Kueng H.J. Schmetterer K.G. Pickl W.F. Lipid rafts, pseudotyping, and virus-like particles: relevance of a novel, configurable, and modular antigen-presenting platform.Int. Arch. Allergy Immunol. 2011; 154: 89-110Crossref PubMed Scopus (12) Google Scholar, 24Pickl W.F. Pimentel-Muinos F.X. Seed B. Lipid rafts and pseudotyping.J. Virol. 2001; 75: 7175-7183Crossref PubMed Scopus (141) Google Scholar). Both reflect physiological sorting mechanisms that are employed to direct the GPI-APs to sites of relevance for biomedical application. MP exploits a specific property of the GPI-Aps, which is the ability of purified GPI-AP preparations to spontaneously reinsert into lipid bilayer membranes (18Metzner C. Kochan F. Dangerfield J.A. Fluorescence molecular painting of enveloped viruses.Mol. Biotechnol. 2013; 53: 9-18Crossref PubMed Scopus (15) Google Scholar, 25Medof M.E. Kinoshita T. Nussenzweig V. Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes.J. Exp. Med. 1984; 160: 1558-1578Crossref PubMed Scopus (448) Google Scholar, 26Medof M.E. Nagarajan S. Tykocinski M.L. Cell-surface engineering with GPI-anchored proteins.FASEB J. 1996; 10: 574-586Crossref PubMed Scopus (181) Google Scholar, 27Nagarajan S. Anderson M. Ahmed S.N. Sell K.W. Selvaraj P. Purification and optimization of functional reconstitution on the surface of leukemic cell lines of GPI-anchored Fc gamma receptor III.J. Immunol. Methods. 1995; 184: 241-251Crossref PubMed Scopus (36) Google Scholar, 28Metzner C. Mostegl M.M. Gunzburg W.H. Salmons B. Dangerfield J.A. Association of glycosylphosphatidylinositol-anchored protein with retroviral particles.FASEB J. 2008; 22: 2734-2739Crossref PubMed Scopus (27) Google Scholar, 29Heider S. Kleinberger S. Kochan F. Dangerfield J.A. Metzner C. Immune protection of retroviral vectors upon molecular painting with the complement regulatory protein CD59.Mol. Biotechnol. 2016; 58: 480-488Crossref PubMed Scopus (4) Google Scholar, 30Bao Q. Niess H. Djafarzadeh R. Zhao Y. Schwarz B. Angele M.K. Jauch K.W. Nelson P.J. Bruns C.J. Recombinant TIMP-1-GPI inhibits growth of fibrosarcoma and enhances tumor sensitivity to doxorubicin.Target. Oncol. 2014; 9: 251-261Crossref PubMed Scopus (10) Google Scholar, 31Muenchmeier N. Boecker S. Bankel L. Hinz L. Rieth N. Lapa C. Mendler A.N. Noessner E. Mocikat R. Nelson P.J. A novel CXCL10-based GPI-anchored fusion protein as adjuvant in NK-based tumor therapy.PLoS One. 2013; 8: e72749Crossref PubMed Scopus (16) Google Scholar, 32Premkumar D.R. Fukuoka Y. Sevlever D. Brunschwig E. Rosenberry T.L. Tykocinski M.L. Medof M.E. Properties of exogenously added GPI-anchored proteins following their incorporation into cells.J. Cell. Biochem. 2001; 82: 234-245Crossref PubMed Scopus (63) Google Scholar, 33Selvaraj P. Dustin M.L. Silber R. Low M.G. Springer T.A. Deficiency of lymphocyte function-associated antigen 3 (LFA-3) in paroxysmal nocturnal hemoglobinuria. Functional correlates and evidence for a phosphatidylinositol membrane anchor.J. Exp. Med. 1987; 166: 1011-1025Crossref PubMed Scopus (101) Google Scholar). Technically, the mixing and incubation of lipid bilayer membranes and a sufficient quantity of purified GPI-APs at 37°C is enough to initiate the process (followed by an optional removal of noninserted protein, i.e., by centrifugation; see Fig. 2). This property of GPI-APs was described for the first time in 1984 (see Fig. 3 for an overview of the development of GPI-AP membrane engineering) and is based on work by Medof, Kinoshita, and Nussenzweig (25Medof M.E. Kinoshita T. Nussenzweig V. Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes.J. Exp. Med. 1984; 160: 1558-1578Crossref PubMed Scopus (448) Google Scholar). In this original study, the human regulator of complement CD55 (or decay-accelerating factor) was purified and found to be inserted into erythrocytes upon coincubation (see Table 1 for an overview of proteins used for GPI-AP membrane engineering). The association was shown to increase in a time- and temperature-dependent manner and the protein's original complement regulatory activity was conserved. Interestingly, the nature of the membrane anchoring of CD55 was not known at the time and only discovered 2 years later (34Medof M.E. Walter E.I. Roberts W.L. Haas R. Rosenberry T.L. Decay accelerating factor of complement is anchored to cells by a C-terminal glycolipid.Biochemistry. 1986; 25: 6740-6747Crossref PubMed Scopus (175) Google Scholar). Carrier lipids and small amounts of detergents seem to enhance the process (19Patel J.M. Kim M.C. Vartabedian V.F. Lee Y.N. He S. Song J.M. Choi H.J. Yamanaka S. Amaram N. Lukacher A. et al.Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses.Nanomedicine. 2015; 11: 1097-1107Crossref PubMed Scopus (19) Google Scholar, 20Legler D.F. Doucey M.A. Schneider P. Chapatte L. Bender F.C. Bron C. Differential insertion of GPI-anchored GFPs into lipid rafts of live cells.FASEB J. 2005; 19: 73-75Crossref PubMed Scopus (98) Google Scholar, 35Patel J.M. Vartabedian V.F. Bozeman E.N. Caoyonan B.E. Srivatsan S. Pack C.D. Dey P. D'Souza M.J. Yang L. Selvaraj P. Plasma membrane vesicles decorated with glycolipid-anchored antigens and adjuvants via protein transfer as an antigen delivery platform for inhibition of tumor growth.Biomaterials. 2016; 74: 231-244Crossref PubMed Scopus (28) Google Scholar, 36Patel J.M. Vartabedian V.F. Kim M.C. He S. Kang S.M. Selvaraj P. Influenza virus-like particles engineered by protein transfer with tumor-associated antigens induces protective antitumor immunity.Biotechnol. Bioeng. 2015; 112: 1102-1110Crossref PubMed Scopus (28) Google Scholar). Inter-cellular transfer of GPI-APs has also been described under physiological conditions: onto maturing sperm cells (37Kirchhoff C. Hale G. Cell-to-cell transfer of glycosylphosphatidylinositol-anchored membrane proteins during sperm maturation.Mol. Hum. Reprod. 1996; 2: 177-184Crossref PubMed Scopus (130) Google Scholar) or, for CD59, from erythrocytes to endothelial cells (38Kooyman D.L. Byrne G.W. McClellan S. Nielsen D. Tone M. Waldmann H. Coffman T.M. McCurry K.R. Platt J.L. Logan J.S. In vivo transfer of GPI-linked complement restriction factors from erythrocytes to the endothelium.Science. 1995; 269: 89-92Crossref PubMed Scopus (220) Google Scholar), as well as for trypanosomal variant surface glycoprotein, to erythrocytes of infected patients (39Rifkin M.R. Landsberger F.R. Trypanosome variant surface glycoprotein transfer to target membranes: a model for the pathogenesis of trypanosomiasis.Proc. Natl. Acad. Sci. USA. 1990; 87: 801-805Crossref PubMed Scopus (79) Google Scholar). However, mechanisms for these protein transfer events may vary and commonly involve extracellular lipid vesicles (40Sullivan R. Frenette G. Girouard J. Epididymosomes are involved in the acquisition of new sperm proteins during epididymal transit.Asian J. Androl. 2007; 9: 483-491Crossref PubMed Scopus (193) Google Scholar, 41Martin-DeLeon P.A. Epididymosomes: transfer of fertility-modulating proteins to the sperm surface.Asian J. Androl. 2015; 17: 720-725Crossref PubMed Scopus (22) Google Scholar, 42Sullivan R. Saez F. Girouard J. Frenette G. Role of exosomes in sperm maturation during the transit along the male reproductive tract.Blood Cells Mol. Dis. 2005; 35: 1-10Crossref PubMed Scopus (238) Google Scholar). Protein transfer processes employing such vesicles would also allow for a degree of specificity, mediated by ligands on the protein donor vesicle and receptors on the acceptor membranes. Very little is known about how MP occurs. Mechanistically, a process where small aggregates of GPI-APs, eventually augmented by carrier lipids or detergent, first fuse with lipid bilayer membranes and then diffuse laterally seems likely. This is supported by the fact that signaling properties of GPI-APs are not restored immediately upon MP. Alternatively, a mechanism involving endocytosis and internal insertion followed by redistribution has been discussed (43Ilangumaran S. Robinson P.J. Hoessli D.C. Transfer of exogenous glycosylphos-phatidylinositol (GPI)-linked molecules to plasma membranes.Trends Cell Biol. 1996; 6: 163-167Abstract Full Text PDF PubMed Scopus (67) Google Scholar). Integration is directly mediated by the fatty acid residues of the GPI anchor. Enzymatic removal effectively abrogates the ability to insert (18Metzner C. Kochan F. Dangerfield J.A. Fluorescence molecular painting of enveloped viruses.Mol. Biotechnol. 2013; 53: 9-18Crossref PubMed Scopus (15) Google Scholar) and insertion is poor at 4°C (25Medof M.E. Kinoshita T. Nussenzweig V. Inhibition of complement activation on the surface of cells after incorporation of decay-accelerating factor (DAF) into their membranes.J. Exp. Med. 1984; 160: 1558-1578Crossref PubMed Scopus (448) Google Scholar). Several routes toward clinical application for MP have been explored since then, including the use of recombinant GPI-anchored CD4 as a strategy for human immunodeficiency virus (HIV)-mediated gene therapy (44Brodsky R.A. Jane S.M. Vanin E.F. Mitsuya H. Peters T.R. Shimada T. Medof M.E. Nienhuis A.W. Purified GPI-anchored CD4DAF as a receptor for HIV-mediated gene transfer.Hum. Gene Ther. 1994; 5: 1231-1239Crossref PubMed Scopus (18) Google Scholar) and the use of the natural, non-recombinantly GPI-AP CD55 and CD59, to treat paroxysmal nocturnal hemoglobinuria (PNH) (45Sloand E.M. Mainwaring L. Keyvanfar K. Chen J. Maciejewski J. Klein H.G. Young N.S. Transfer of glycosylphosphatidylinositol-anchored proteins to deficient cells after erythrocyte transfusion in paroxysmal nocturnal hemoglobinuria.Blood. 2004; 104: 3782-3788Crossref PubMed Scopus (39) Google Scholar, 46Hill A. Ridley S.H. Esser D. Oldroyd R.G. Cullen M.J. Kareclas P. Gallagher S. Smith G.P. Richards S.J. White J. et al.Protection of erythrocytes from human complement-mediated lysis by membrane-targeted recombinant soluble CD59: a new approach to PNH therapy.Blood. 2006; 107: 2131-2137Crossref PubMed Scopus (45) Google Scholar). In PNH, a defect in GPI anchoring leads to an enhanced susceptibility to the complement system. Also, approaches toward tumor therapy and vaccination using GPI-anchored variants of the costimulatory molecule, B7.1 (47McHugh R.S. Ahmed S.N. Wang Y.C. Sell K.W. Selvaraj P. Construction, purification, and functional incorporation on tumor cells of glycolipid-anchored human B7-1 (CD80).Proc. Natl. Acad. Sci. USA. 1995; 92: 8059-8063Crossref PubMed Scopus (104) Google Scholar, 48McHugh R.S. Nagarajan S. Wang Y.C. Sell K.W. Selvaraj P. Protein transfer of glycosyl-phosphatidylinositol-B7–1 into tumor cell membranes: a novel approach to tumor immunotherapy.Cancer Res. 1999; 59: 2433-2437PubMed Google Scholar), the cytokines, interleukin (IL)2 (49Spurny B. Optimization of Delivery of Functional GPI-IL2 to Virus-like Particles Using Molecular Painting.BSc Dissertation. University of Veterinary Medicine, Vienna2014Google Scholar, 50Schöchtner S. Molecular Painting of HIV-1 Virus-like Particles with Interleukin-2 for Immune Stimulation.in: MSc Dissertation. University of Veterinary Medicine, Vienna2014: 148-164Google Scholar) and IL12 (51Selvaraj P. Yerra A. Tien L. Shashidharamurthy R. Custom designing therapeutic cancer vaccines: delivery of immunostimulatory molecule adjuvants by protein transfer.Hum. Vaccin. 2008; 4: 384-388Crossref PubMed Scopus (8) Google Scholar, 52Nagarajan S. Selvaraj P. Human tumor membrane vesicles modified to express glycolipid-anchored IL-12 by protein transfer induce T cell proliferation in vitro: a potential approach for local delivery of cytokines during vaccination.Vaccine. 2006; 24: 2264-2274Crossref PubMed Scopus (27) Google Scholar, 53Nagarajan S. Selvaraj P. Glycolipid-anchored IL-12 expressed on tumor cell surface induces antitumor immune response.Cancer Res. 2002; 62: 2869-2874PubMed Google Scholar), granulocyte/macrophage-colony stimulating factor (GM-CSF) (19Patel J.M. Kim M.C. Vartabedian V.F. Lee Y.N. He S. Song J.M. Choi H.J. Yamanaka S. Amaram N. Lukacher A. et al.Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses.Nanomedicine. 2015; 11: 1097-1107Crossref PubMed Scopus (19) Google Scholar), the human epidermal growth factor (EGF) receptor 2 (HER2) tumor antigen (36Patel J.M. Vartabedian V.F. Kim M.C. He S. Kang S.M. Selvaraj P. Influenza virus-like particles engineered by protein transfer with tumor-associated antigens induces protective antitumor immunity.Biotechnol. Bioeng. 2015; 112: 1102-1110Crossref PubMed Scopus (28) Google Scholar), and the intercellular adhesion molecule, (ICAM)1 (CD54) (19Patel J.M. Kim M.C. Vartabedian V.F. Lee Y.N. He S. Song J.M. Choi H.J. Yamanaka S. Amaram N. Lukacher A. et al.Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses.Nanomedicine. 2015; 11: 1097-1107Crossref PubMed Scopus (19) Google Scholar), were undertaken. The MP process was adapted for the modification of enveloped viral particles in 2008, originally employing lenti- and γretroviral particle-derived gene therapy vectors (28Metzner C. Mostegl M.M. Gunzburg W.H. Salmons B. Dangerfield J.A. Association of glycosylphosphatidylinositol-anchored protein with retroviral particles.FASEB J. 2008; 22: 2734-2739Crossref PubMed Scopus (27) Google Scholar). Later the range of viral species was expanded to orthomyxo- and herpesviral particles, as well as the range of modifying proteins, to GPI-anchored variants of green fluorescent protein (GFP) (18Metzner C. Kochan F. Dangerfield J.A. Fluorescence molecular painting of enveloped viruses.Mol. Biotechnol. 2013; 53: 9-18Crossref PubMed Scopus (15) Google Scholar), the red fluorescent protein tdTomato (54Shaner N.C. Campbell R.E. Steinbach P.A. Giepmans B.N. Palmer A.E. Tsien R.Y. Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein.Nat. Biotechnol. 2004; 22: 1567-1572Crossref PubMed Scopus (3499) Google Scholar), EGF (55Kochan F. Dangerfield J.A. Gunzburg W.H. Salmons B. Metzner C. A modular system for transduction targeting of viral vectors for gene therapy.Hum. Gene Ther. 2012; 23: A126Google Scholar), the HIV receptor CD4 (55Kochan F. Dangerfield J.A. Gunzburg W.H. Salmons B. Metzner C. A modular system for transduction targeting of viral vectors for gene therapy.Hum. Gene Ther. 2012; 23: A126Google Scholar), and IL2 (49Spurny B. Optimization of Delivery of Functional GPI-IL2 to Virus-like Particles Using Molecular Painting.BSc Dissertation. University of Veterinary Medicine, Vienna2014Google Scholar, 50Schöchtner S. Molecular Painting of HIV-1 Virus-like Particles with Interleukin-2 for Immune Stimulation.in: MSc Dissertation. University of Veterinary Medicine, Vienna2014: 148-164Google Scholar). The ability of the virus or virus vector to infect is not necessarily hindered as a consequence of insertion (28Metzner C. Mostegl M.M. Gunzburg W.H. Salmons B. Dangerfield J.A. Association of glycosylphosphatidylinositol-anchored protein with retroviral particles.FASEB J. 2008; 22: 2734-2739Crossref PubMed Scopus (27) Google Scholar). However, caution is advised because reductions in infectivity due to the presence of additional proteins on the envelope are possible under certain circumstances (29Heider S. Kleinberger S. Kochan F. Dangerfield J.A. Metzner C. Immune protection of retroviral vectors upon molecular painting with the complement regulatory protein CD59.Mol. Biotechnol. 2016; 58: 480-488Crossref PubMed Scopus (4) Google Scholar). The process is strictly dependent on the
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