Current Progress of Virus-mimicking Nanocarriers for Drug Delivery

Nanomedicines often involve the use of nanocarriers as a delivery system for drugs or genes for maximizing the therapeutic effect and/or minimizing the adverse effect. From drug administration to therapeutic activity, nanocarriers must evade the host's immune system, specifically and efficiently target and enter the cell, and release their payload into the cell cytoplasm by endosomal escape. These processes constitute the early infection stage of viruses. Viruses are a powerful natural nanomaterial for the efficient delivery of genetic information by sophisticated mechanisms. Over the past two decades, many virus-inspired nanocarriers have been generated to permit successful drug and gene delivery. In this review, we summarize the early infection machineries of viruses, of which the part has so far been utilized for delivery systems. Furthermore, we describe basics and applications of the bio-nanocapsule, which is a hepatitis B virus-mimicking nanoparticle harboring nearly all activities involved in the early infection machineries (i.e., stealth activity, targeting activity, cell entry activity, endosomal escaping activity).

[1]  Deborah Fass,et al.  Core Structure of gp41 from the HIV Envelope Glycoprotein , 1997, Cell.

[2]  S. Kuroda,et al.  Development of a virus-mimicking nanocarrier for drug delivery systems: The bio-nanocapsule. , 2015, Advanced drug delivery reviews.

[3]  Mark A. Kay,et al.  Progress and problems with the use of viral vectors for gene therapy , 2003, Nature Reviews Genetics.

[4]  C. Sureau,et al.  Role of the Antigenic Loop of the Hepatitis B Virus Envelope Proteins in Infectivity of Hepatitis Delta Virus , 2005, Journal of Virology.

[5]  S. Kuroda,et al.  Hepatitis B virus envelope L protein particles. Synthesis and assembly in Saccharomyces cerevisiae, purification and characterization. , 1992, The Journal of biological chemistry.

[6]  Ivan R. Nabi,et al.  Caveolae/raft-dependent endocytosis , 2003, The Journal of cell biology.

[7]  P. Stewart,et al.  Role of αv Integrins in Adenovirus Cell Entry and Gene Delivery , 1999, Microbiology and Molecular Biology Reviews.

[8]  P. Bolhuis,et al.  Self-assembly of microcapsules via colloidal bond hybridization and anisotropy , 2015, Nature.

[9]  P. Stewart,et al.  Role of alpha(v) integrins in adenovirus cell entry and gene delivery. , 1999, Microbiology and molecular biology reviews : MMBR.

[10]  Harvey T. McMahon,et al.  Molecular mechanism and physiological functions of clathrin-mediated endocytosis , 2011, Nature Reviews Molecular Cell Biology.

[11]  L. Pelkmans,et al.  Ameobal Pathogen Mimivirus Infects Macrophages through Phagocytosis , 2008, PLoS pathogens.

[12]  John J Rossi,et al.  RNAi and small interfering RNAs in human disease therapeutic applications. , 2010, Trends in biotechnology.

[13]  Ari Helenius,et al.  Virus entry by macropinocytosis , 2009, Nature Cell Biology.

[14]  Y. Kaneda,et al.  Increased expression of DNA cointroduced with nuclear protein in adult rat liver , 1995, Journal of Molecular Medicine.

[15]  J. Ott,et al.  Complement Factor H Polymorphism in Age-Related Macular Degeneration , 2005, Science.

[16]  I. Rodrı́guez-Crespo,et al.  Prediction of a putative fusion peptide in the S protein of hepatitis B virus. , 1994, The Journal of general virology.

[17]  P. Spear,et al.  Herpesviruses and heparan sulfate: an intimate relationship in aid of viral entry. , 2001, The Journal of clinical investigation.

[18]  G. Nemerow,et al.  Adenovirus Protein VI Mediates Membrane Disruption following Capsid Disassembly , 2005, Journal of Virology.

[19]  A. Budkowska,et al.  Hepatitis C virus cell entry: role of lipoproteins and cellular receptors. , 2009, The Journal of general virology.

[20]  N. Lurain,et al.  Host cell-derived complement control proteins CD55 and CD59 are incorporated into the virions of two unrelated enveloped viruses. Human T cell leukemia/lymphoma virus type I (HTLV-I) and human cytomegalovirus (HCMV). , 1995, Journal of immunology.

[21]  P. Choyke,et al.  Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. , 2008, Nanomedicine.

[22]  G. Trugnan,et al.  Rotavirus-Like Particles: A Novel Nanocarrier for the Gut , 2010, Journal of biomedicine & biotechnology.

[23]  T. Tuschl,et al.  Endogenous MHC Class II Processing of a Viral Nuclear Antigen After Autophagy , 2005, Science.

[24]  A. Cuconati,et al.  Hepatitis B Virus , 2017, Methods in Molecular Biology.

[25]  Wenhui Li,et al.  Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus , 2012, eLife.

[26]  R. Hancock,et al.  Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies , 2006, Nature Biotechnology.

[27]  E. Wiertz,et al.  Viral immune evasion: a masterpiece of evolution , 2002, Immunogenetics.

[28]  R. Dwek,et al.  Glycosylation and the immune system. , 2001, Science.

[29]  E. Hildt,et al.  Novel cell permeable motif derived from the PreS2-domain of hepatitis-B virus surface antigens , 2000, Gene Therapy.

[30]  D. Carey,et al.  Syndecans: multifunctional cell-surface co-receptors. , 1997, The Biochemical journal.

[31]  N. Steinmetz,et al.  Biodistribution, pharmacokinetics, and blood compatibility of native and PEGylated tobacco mosaic virus nano-rods and -spheres in mice. , 2014, Virology.

[32]  C. Cho,et al.  Hybrid of baculovirus and galactosylated PEI for efficient gene carrier. , 2009, Virology.

[33]  H. Yagi,et al.  Human Liver-Specific Nanocarrier in a Novel Mouse Xenograft Model Bearing Noncancerous Human Liver Tissue , 2010, European Surgical Research.

[34]  S. Roche,et al.  Structure of the Prefusion Form of the Vesicular Stomatitis Virus Glycoprotein G , 2007, Science.

[35]  J. Schiller,et al.  A Membrane-Destabilizing Peptide in Capsid Protein L2 Is Required for Egress of Papillomavirus Genomes from Endosomes , 2006, Journal of Virology.

[36]  David F. Smith,et al.  Human Parainfluenza Viruses hPIV1 and hPIV3 Bind Oligosaccharides with α2-3-Linked Sialic Acids That Are Distinct from Those Bound by H5 Avian Influenza Virus Hemagglutinin , 2007, Journal of Virology.

[37]  B. Rothen‐Rutishauser,et al.  Targeting her-2/neu with antirat Neu virosomes for cancer therapy. , 2002, Cancer research.

[38]  W. Oyen,et al.  Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes. , 2000, The Journal of pharmacology and experimental therapeutics.

[39]  K. Zatloukal,et al.  Influenza virus hemagglutinin HA-2 N-terminal fusogenic peptides augment gene transfer by transferrin-polylysine-DNA complexes: toward a synthetic virus-like gene-transfer vehicle. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Shiroh Futaki,et al.  Development of a non-viral multifunctional envelope-type nano device by a novel lipid film hydration method. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[41]  A. Ullrich,et al.  Paul Ehrlich's magic bullet concept: 100 years of progress , 2008, Nature Reviews Cancer.

[42]  E. Wagner,et al.  Rhinovirus-mediated endosomal release of transfection complexes , 1995, Journal of virology.

[43]  T. Friedmann,et al.  Enhanced Gene Transfer with Fusogenic Liposomes Containing Vesicular Stomatitis Virus G Glycoprotein , 1998, Journal of Virology.

[44]  R. Iozzo Matrix proteoglycans: from molecular design to cellular function. , 1998, Annual review of biochemistry.

[45]  H. Müller-Eberhard,et al.  Molecular organization and function of the complement system. , 1988, Annual review of biochemistry.

[46]  T. Heath,et al.  FORMATION OF VIROSOMES FROM INFLUENZA SUBUNITS AND LIPOSOMES , 1975, The Lancet.

[47]  E. Blanchard,et al.  Hepatitis C Virus Entry Depends on Clathrin-Mediated Endocytosis , 2006, Journal of Virology.

[48]  L. Yang,et al.  Barrel-stave model or toroidal model? A case study on melittin pores. , 2001, Biophysical journal.

[49]  A. Kondo,et al.  Nanoparticles for the delivery of genes and drugs to human hepatocytes , 2003, Nature Biotechnology.

[50]  R. Ritchie,et al.  Bioinspired structural materials. , 2014, Nature Materials.

[51]  Charles M. Rice,et al.  Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry , 2007, Nature.

[52]  K. Wooley,et al.  Strategies Toward Well-Defined Polymer Nanoparticles Inspired by Nature: Chemistry versus Versatility. , 2012, Journal of polymer science. Part A, Polymer chemistry.

[53]  B. Yélamos,et al.  Study of the putative fusion regions of the preS domain of hepatitis B virus. , 2015, Biochimica et biophysica acta.

[54]  E. Choi,et al.  Efficient and rapid purification of drug- and gene-carrying bio-nanocapsules, hepatitis B virus surface antigen L particles, from Saccharomyces cerevisiae. , 2011, Protein expression and purification.

[55]  J. Galama,et al.  Coxsackievirus protein 2B modifies endoplasmic reticulum membrane and plasma membrane permeability and facilitates virus release , 1997, The EMBO journal.

[56]  A. Zuckerman,et al.  Vaccine-induced escape mutant of hepatitis B virus , 1990, The Lancet.

[57]  J. Wixon,et al.  Gene therapy clinical trials worldwide 1989–2004—an overview , 2004, The journal of gene medicine.

[58]  C. Guguen-Guillouzo,et al.  Myristylation of the hepatitis B virus large surface protein is essential for viral infectivity. , 1995, Virology.

[59]  G. Kotwal Poxviral mimicry of complement and chemokine system components: what's the end game? , 2000, Immunology today.

[60]  Gustaf E. Rydell,et al.  Hepatitis B surface antigen on subviral particles reduces the neutralizing effect of anti-HBs antibodies on hepatitis B viral particles in vitro. , 2017, Virology.

[61]  G. Whittaker,et al.  Fusion of Enveloped Viruses in Endosomes , 2016, Traffic.

[62]  Charles M. Rice,et al.  Human occludin is a hepatitis C virus entry factor required for infection of mouse cells , 2009, Nature.

[63]  Ernst Wagner,et al.  Optimizing targeted gene delivery: Chemical modification of viral vectors and synthesis of artificial virus vector systems , 2006, The AAPS Journal.

[64]  Ari Helenius,et al.  Virus entry by endocytosis. , 2010, Annual review of biochemistry.

[65]  Trevor Douglas,et al.  Viruses: Making Friends with Old Foes , 2006, Science.

[66]  S. Dowdy Overcoming cellular barriers for RNA therapeutics , 2017, Nature Biotechnology.

[67]  Jesse V Jokerst,et al.  Nanoparticle PEGylation for imaging and therapy. , 2011, Nanomedicine.

[68]  P. Cullis,et al.  Drug Delivery Systems: Entering the Mainstream , 2004, Science.

[69]  F. Chisari,et al.  To kill or to cure: options in host defense against viral infection. , 1996, Current opinion in immunology.

[70]  G. Nybakken,et al.  West Nile virus nonstructural protein NS1 inhibits complement activation by binding the regulatory protein factor H , 2006, Proceedings of the National Academy of Sciences.

[71]  Kinam Park,et al.  Targeted drug delivery to tumors: myths, reality and possibility. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[72]  Xiaoyang Xu,et al.  Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. , 2014, Advanced drug delivery reviews.

[73]  Kazunori Kataoka,et al.  Progress of drug-loaded polymeric micelles into clinical studies. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[74]  M. Dierich,et al.  Efficient destruction of human immunodeficiency virus in human serum by inhibiting the protective action of complement factor H and decay accelerating factor (DAF, CD55) , 1996, The Journal of experimental medicine.

[75]  J. Skehel,et al.  Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. , 2000, Annual review of biochemistry.

[76]  M. Houghton,et al.  Binding of hepatitis C virus to CD81. , 1998, Science.

[77]  V. Venditto,et al.  Cancer nanomedicines: so many papers and so few drugs! , 2013, Advanced drug delivery reviews.

[78]  Wim E. Hennink,et al.  Artificial viruses: a nanotechnological approach to gene delivery , 2006, Nature Reviews Drug Discovery.

[79]  U. Greber,et al.  Adenovirus triggers macropinocytosis and endosomal leakage together with its clathrin-mediated uptake , 2002, The Journal of cell biology.

[80]  Masumi Iijima,et al.  Intracellular trafficking of bio-nanocapsule-liposome complex: Identification of fusogenic activity in the pre-S1 region of hepatitis B virus surface antigen L protein. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[81]  J. Atabekov,et al.  Thermal transition of native tobacco mosaic virus and RNA-free viral proteins into spherical nanoparticles. , 2011, The Journal of general virology.

[82]  S M Moghimi,et al.  Long-circulating and target-specific nanoparticles: theory to practice. , 2001, Pharmacological reviews.

[83]  H. Maeda,et al.  A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. , 1986, Cancer research.

[84]  A. Kidd,et al.  Adenovirus Type 37 Uses Sialic Acid as a Cellular Receptor , 2000, Journal of Virology.

[85]  Junichi Nakai,et al.  Vaccinia Virus Uses Macropinocytosis and Apoptotic Mimicry to Enter Host Cells , 2008 .

[86]  W. Carman,et al.  Loss of the common "A" determinant of hepatitis B surface antigen by a vaccine-induced escape mutant. , 1992, The Journal of clinical investigation.

[87]  H. Geuze,et al.  Human Macrophages Accumulate HIV‐1 Particles in MHC II Compartments , 2002, Traffic.

[88]  C. Schwegmann-Wessels,et al.  Sialic acids as receptor determinants for coronaviruses , 2006, Glycoconjugate Journal.

[89]  J. Behr,et al.  Gene transfer with synthetic virus-like particles via the integrin-mediated endocytosis pathway , 1999, Gene Therapy.

[90]  H. Ploegh Viral strategies of immune evasion. , 1998, Science.

[91]  T. Geijtenbeek,et al.  Syndecan-3 is a dendritic cell-specific attachment receptor for HIV-1 , 2007, Proceedings of the National Academy of Sciences.

[92]  Samir Mitragotri,et al.  Role of target geometry in phagocytosis. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[93]  L. Lopalco,et al.  HIV glycoprotein 41 and complement factor H interact with each other and share functional as well as antigenic homology. , 1995, AIDS research and human retroviruses.

[94]  Dong Chen,et al.  The shape effect of mesoporous silica nanoparticles on biodistribution, clearance, and biocompatibility in vivo. , 2011, ACS nano.

[95]  M. Zerial,et al.  rab5 controls early endosome fusion in vitro , 1991, Cell.

[96]  A. Helenius,et al.  On the entry of semliki forest virus into BHK-21 cells , 1980, The Journal of cell biology.

[97]  In‐San Kim,et al.  Bioengineered protein-based nanocage for drug delivery. , 2016, Advanced drug delivery reviews.

[98]  T. Graule,et al.  Isoelectric points of viruses , 2009, Journal of applied microbiology.

[99]  Joohee Jung,et al.  Bio-nanocapsule conjugated with liposomes for in vivo pinpoint delivery of various materials. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[100]  F. Deist,et al.  Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. , 2000, Science.

[101]  T. Ishida,et al.  Anti-PEG IgM Response against PEGylated Liposomes in Mice and Rats , 2010, Pharmaceutics.

[102]  R. Bartenschlager,et al.  Replication of hepatitis C virus. , 2000, The Journal of general virology.

[103]  R. Wagner,et al.  Virus-like particles—universal molecular toolboxes , 2007, Current Opinion in Biotechnology.

[104]  A. Helenius,et al.  Fusion of Semliki forest virus with the plasma membrane can be induced by low pH , 1980, The Journal of cell biology.

[105]  V. Torchilin,et al.  TAT peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[106]  Sarah Seifert,et al.  Image-based analysis of lipid nanoparticle–mediated siRNA delivery, intracellular trafficking and endosomal escape , 2013, Nature Biotechnology.

[107]  P. Cullis,et al.  Liposomal drug delivery systems: from concept to clinical applications. , 2013, Advanced drug delivery reviews.

[108]  Y Ikada,et al.  Effect of the size and surface charge of polymer microspheres on their phagocytosis by macrophage. , 1988, Biomaterials.

[109]  R. Nolte,et al.  Temperature‐Switchable Assembly of Supramolecular Virus–Polymer Complexes , 2011 .

[110]  R. Samulski,et al.  Membrane-Associated Heparan Sulfate Proteoglycan Is a Receptor for Adeno-Associated Virus Type 2 Virions , 1998, Journal of Virology.

[111]  Samir Mitragotri,et al.  Role of Particle Size in Phagocytosis of Polymeric Microspheres , 2008, Pharmaceutical Research.

[112]  K. P. Murphy,et al.  Janeway's immunobiology , 2007 .

[113]  Charles M. Rice,et al.  The ins and outs of hepatitis C virus entry and assembly , 2013, Nature Reviews Microbiology.

[114]  Zhenghong Yuan,et al.  Gene delivery into hepatocytes with the preS/liposome/DNA system , 2008, Biotechnology journal.

[115]  P. Cicuta,et al.  Phagocytosis dynamics depends on target shape. , 2013, Biophysical journal.

[116]  E. Damonte,et al.  Functional entry of dengue virus into Aedes albopictus mosquito cells is dependent on clathrin-mediated endocytosis. , 2008, The Journal of general virology.

[117]  J. Wilschut,et al.  Virosome-mediated delivery of protein antigens to dendritic cells. , 2002, Vaccine.

[118]  M. Mano,et al.  Cell-Penetrating Peptides—Mechanisms of Cellular Uptake and Generation of Delivery Systems , 2010, Pharmaceuticals.

[119]  R. Bartenschlager,et al.  A Slow Maturation Process Renders Hepatitis B Virus Infectious. , 2016, Cell host & microbe.

[120]  Arezou A Ghazani,et al.  Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. , 2006, Nano letters.

[121]  M. Hashizume,et al.  Expression and characterization of myristoylated preS1-conjugated nanocages for targeted cell delivery. , 2015, Protein expression and purification.

[122]  N. Pochet,et al.  A targeted functional RNA interference screen uncovers glypican 5 as an entry factor for hepatitis B and D viruses , 2016, Hepatology.

[123]  C. Sureau,et al.  A conformational heparan sulfate binding site essential to infectivity overlaps with the conserved hepatitis B virus A‐determinant , 2013, Hepatology.

[124]  E. Choi,et al.  Hepatitis B virus envelope L protein-derived bio-nanocapsules: mechanisms of cellular attachment and entry into human hepatic cells. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[125]  M. Imamura,et al.  Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor , 2011, Nature Medicine.

[126]  R. Cortese,et al.  The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus , 2002, The EMBO journal.

[127]  M. Carroll,et al.  The complement system in regulation of adaptive immunity , 2004, Nature Immunology.

[128]  Tomoyuki Nishikawa,et al.  Hemagglutinating virus of Japan (HVJ) envelope vector as a versatile gene delivery system. , 2002, Molecular therapy : the journal of the American Society of Gene Therapy.

[129]  J. Navaza,et al.  The Fusion Glycoprotein Shell of Semliki Forest Virus An Icosahedral Assembly Primed for Fusogenic Activation at Endosomal pH , 2001, Cell.

[130]  P. Hilgard,et al.  Heparan sulfate proteoglycans initiate dengue virus infection of hepatocytes , 2000, Hepatology.

[131]  K. Kirkegaard,et al.  Remodeling the Endoplasmic Reticulum by Poliovirus Infection and by Individual Viral Proteins: an Autophagy-Like Origin for Virus-Induced Vesicles , 2000, Journal of Virology.

[132]  M. Marsh,et al.  The cell biology of receptor-mediated virus entry , 2011, The Journal of cell biology.

[133]  E. Choi,et al.  Virosomes of hepatitis B virus envelope L proteins containing doxorubicin: synergistic enhancement of human liver-specific antitumor growth activity by radiotherapy , 2015, International journal of nanomedicine.

[134]  C. Malboeuf,et al.  Human papillomavirus-like particles mediate functional delivery of plasmid DNA to antigen presenting cells in vivo. , 2007, Vaccine.

[135]  A. Alcamí,et al.  Viral mechanisms of immune evasion , 2000, Immunology Today.

[136]  Duane E. Prasuhn,et al.  Bio-distribution, toxicity and pathology of cowpea mosaic virus nanoparticles in vivo. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[137]  D. Metzger,et al.  Fc Receptor-Mediated Phagocytosis Makes a Significant Contribution to Clearance of Influenza Virus Infections1 , 2001, The Journal of Immunology.

[138]  Robert G Parton,et al.  Clathrin-independent endocytosis: new insights into caveolae and non-caveolar lipid raft carriers. , 2005, Biochimica et biophysica acta.

[139]  Y. Kaneda,et al.  Virosomes: evolution of the liposome as a targeted drug delivery system. , 2000, Advanced drug delivery reviews.

[140]  S. Kuroda,et al.  Identification of polymerized-albumin receptor domain in the pre-S2 region of hepatitis B virus surface antigen M protein. , 1992, Journal of biotechnology.

[141]  R. Bartenschlager,et al.  Strategies to inhibit entry of HBV and HDV into hepatocytes. , 2014, Gastroenterology.

[142]  A. J. Tavares,et al.  Analysis of nanoparticle delivery to tumours , 2016 .

[143]  W. DeGrado,et al.  Membrane binding and conformational properties of peptides representing the NH2 terminus of influenza HA-2. , 1987, The Journal of biological chemistry.

[144]  Hamidreza Ghandehari,et al.  Geometry and surface characteristics of gold nanoparticles influence their biodistribution and uptake by macrophages. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[145]  Xuanmiao Zhang,et al.  Hepatitis B virus preS1-derived lipopeptide functionalized liposomes for targeting of hepatic cells. , 2014, Biomaterials.

[146]  S. Cusack,et al.  Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid , 1988, Nature.

[147]  S. Kuroda,et al.  Cellular uptake of hepatitis B virus envelope L particles is independent of sodium taurocholate cotransporting polypeptide, but dependent on heparan sulfate proteoglycan. , 2016, Virology.

[148]  Lisa Brannon-Peppas,et al.  Active targeting schemes for nanoparticle systems in cancer therapeutics. , 2008, Advanced drug delivery reviews.

[149]  Pratip K. Chattopadhyay,et al.  The Size of the Viral Inoculum Contributes to the Outcome of Hepatitis B Virus Infection , 2009, Journal of Virology.

[150]  Benjamin J. Briggs,et al.  Role of clathrin-mediated endocytosis during vesicular stomatitis virus entry into host cells. , 2005, Virology.

[151]  J. Esko,et al.  Heparan sulfate proteoglycans. , 2011, Cold Spring Harbor perspectives in biology.

[152]  J. M. Harris,et al.  Effect of pegylation on pharmaceuticals , 2003, Nature Reviews Drug Discovery.

[153]  Dominic J. Glover,et al.  Multifunctional protein nanocarriers for targeted nuclear gene delivery in nondividing cells , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[154]  F. Chisari,et al.  Stealth and Cunning: Hepatitis B and Hepatitis C Viruses , 2005, Journal of Virology.

[155]  S. Urban,et al.  Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycans. , 2007, Hepatology.