Gregory Gregoriadis – författare

The NATO Advanced Studies Institute series "Targeting of Drugs" was originated in 1981. It is now a major international forum, held every two years in Cape Sounion, Greece, in which the present and the future of this important area of research in drug delivery is discussed in great depth. Previous ASIs of the series dealt with drug carriers of natural and synthetic origin, their interaction with the biological milieu, ways by which the latter influences such interaction, strategies by which milieu interference curtailing the function of drug carriers is circumvented and, more recently, with the application of drug carriers for the delivery of peptides and proteins. The present book contains the of the 7th NATO ASI "Targeting of Drugs: Advances in System Constructs", proceedings held in Cape Sounion during 24 June -5 July 1993. As the title implies, the book deals with a variety of approaches to carrier design or modification that contribute to optimal carrier function. to Mrs Concha Perring for her assistance with the We express our appreciation organization of the ASI. We thank Dr. G. Deliconstantinos who, as chairperson of the Local Committee, contributed to the success of the Institute. The ASI was held under the sponsorship of NATO Scientific Affairs Division and co-sponsored and generously financed by SmithKline Beecham Pharmaceuticals (King of Prussia). Financial assistance was also provided by Liposome Technology Inc. (Menlo Park), Vestar Inc. (San Dimas) and Zeneka (Macclesfield).

During the last decade or so vaccine development has been facilitated by rapid advances in molecular and cell biology. These have laid the foundations of a new generation of vaccines exemplified by subunit vaccines produced through gene cloning and by synthetic peptides mimicking small regions of proteins on the outer coat of viruses. Such peptide~ are capable of eliciting virus-neutralizing antibodies. Unfortunately, subunit and peptide vaccines are only weakly or non immunogenic in the absence of immunological adjuvants that are known to augment specific cell-mediated immune responses to the antigens and to promote the formation of protective antibodies. This book contains the proceedings of the 4th NATO Advanced Studies Institute (ASI) "Vaccines: New Generation Immunological Adjuvants" held at Cape Sounion Beach, Greece, during 24 June -5 . July 1994 and deals in depth with both theoretical and practical aspects of vaccinology. These include the role of antigen presenting cells in the induction of immune responses. immunopotentiation by a variety of new generation immunological adjuvants and vaccine carriers. and recent advances and perspectives in experimental vaccines as well as vaccinatioll with nucleic acids. We express our appreciation to Dr. K. Dalsgaard and Dr. J. L. Virelizier for their cooperatioll in planning the ASI and to Mrs. Concha Pening for her excellent production of the manuscripts. The ASI was held under the sponsorship of NATO Scientific Affairs Division and generously co-sponsored by SmithKline Beecham Pharmaceuticals (Philadelphia).

Proceedings of a NATO ASI held in Cape Sounion, Greece, June 24-July 5, 1995

During the last decade or so vaccine development has been facilitated by rapid ad- vances in the molecular and cell biology ofthe immune system. This has laid the foundations of a new generation of vaccines exemplified by subunit vaccines produced through gene cloning and by synthetic peptides mimicking small regions ofproteins on the outer coat ofvi- ruses. However, as subunit and peptide vaccines are only weakly or non-immunogenic, there is areal need for strategies to improve their potency. This book contains the proceedings of the 5th NATO Advanced Studies Institute (ASI), "Vaccine Design: The Role of Cytokine Networks," held at Cape Sounion Beach, Greece, during 24 June-5 July 1996 and deals in depth with the role ofbasic immunology in the regulation of immunity and vaccine design. Special emphasis is given to the use of cyto- kines in conjuction with vaccines with the aim ofimproving their potency or the use ofvac- cines designed to improve cytokine production. We express our appreciation to Dr. J.-L. Virelizier and Dr. G. Kollias for their cooperation in planning the ASI and to Mrs. Concha Perring for her excellent production ofthe manuscripts.The ASI was held under the sponsor- ship of NATO Scientific Affairs Division and generously co-sponsored by SmithKline Beecham Pharmaceuticals (Philadelphia). Financial assistance was also provided by Connaught Laboratories Ltd. (Ontario), Pasteur Merieux (Marcy I 'Etoile), Biochine (Siena), Help SA (Athens), and Avanti Polar Lipids Inc. (Birmingham, USA).

The NATO Advanced Studies Institute series "Targeting of Drugs" was originated in 1981. It is now a major international forum, held every two years in Cape Sounion, Greece, in which the present and the future of this important area of research in drug delivery is discussed in great depth. Previous ASIs of the series dealt with drug carriers of natural and synthetic origin, their interactions with the biological milieu, ways by which milieu interference is circumvented, approaches to carrier design or modification that contribute to optimal carrier function, and, more recently, with strategies for gene and oligonucleotide delivery in therapy The present book contains the proceedings of the 9th NATO ASI, "Targeting of Drugs: Strategies for Stealth Therapeutic Systems", held in Cape Sounion during 24 June -5 July 1997. As the title implies, the book deals with a variety of approaches to evade the reticuloendothelial system and thus extend the circulation time of a variety of delivery systems including polymers, biopolymers, liposomes, and other nanoparticles or microparticles. We express our appreciation to Mrs. Concha Perring for her assistance with the organization of the AS!.The ASI was held under the sponsorship of NATO Scientific Affairs Division and supported by Sequus Pharmaceuticals (Menlo Park, CA, USA), The Liposome Company (Princeton, NJ, USA), NOVO Nordisk (Bagsvaard, Denmark), NeXstar Pharmaceuticals (Boulder, CO, USA), Gene Medicine (Houston, TX, USA), Pfizer Ltd (Sandwich, Kent, UK), Merck (Rahway, NJ, USA), and Biovation Ltd (Aberdeen, UK).

Liposome Technology, Volume III: Interactions of Liposomes with the Biological Milieu, Third Edition, is a comprehensively updated and expanded new edition of a classic text in the field. Including step-by-step technical details, Volume III describes technologies for yielding liposomes that can function in a targeted fashion, and highlights methods for studying the interaction of liposomes within the biological environment to be applied in the detection, therapy, or prevention of disease. This source also offers critical discussions of the methodologies of each technology described so that readers can examine the benefits and limitations and compare it to other approaches.

Liposome Technology, Volume I: Liposome Preparation and Related Techniques, Third Edition, is a thoroughly updated and expanded new edition of a classic text in the field. Including step-by-step technical details, Volume I illustrates numerous methods for liposome preparation and auxiliary techniques necessary for the stabilization and characterization of liposomes. This source also offers critical discussions of the methodologies of each technology described so that readers can examine the benefits and limitations and compare it to other approaches.

Liposome Technology, Volume II: Entrapment of Drugs and Other Materials into Liposomes, Third Edition is a comprehensively updated and expanded new edition of a classic text in the field. Including step-by-step technical details, Volume II describes procedures for the incorporation of drugs and other materials into liposomes for a variety therapeutics, chosen because of their relevance to current trends in liposome applications or because they represent groups of active pharmaceutical ingredients with similar physical and chemical properties. This source also offers critical discussions of the methodologies of each technology described so that readers can examine the benefits and limitations and compare it to other approaches.

Liposome Technology, Volume III: Interactions of Liposomes with the Biological Milieu, Third Edition, is a comprehensively updated and expanded new edition of a classic text in the field. Including step-by-step technical details, Volume III describes technologies for yielding liposomes that can function in a targeted fashion, and highlights methods for studying the interaction of liposomes within the biological environment to be applied in the detection, therapy, or prevention of disease. This source also offers critical discussions of the methodologies of each technology described so that readers can examine the benefits and limitations and compare it to other approaches.

Liposome Technology, Volume I: Liposome Preparation and Related Techniques, Third Edition, is a thoroughly updated and expanded new edition of a classic text in the field. Including step-by-step technical details, Volume I illustrates numerous methods for liposome preparation and auxiliary techniques necessary for the stabilization and characteriza

Liposome Technology, Volume II: Entrapment of Drugs and Other Materials into Liposomes, Third Edition is a comprehensively updated and expanded new edition of a classic text in the field. Including step-by-step technical details, Volume II describes procedures for the incorporation of drugs and other materials into liposomes for a variety therapeut

Liposome Technology, Volume I: Liposome Preparation and Related Techniques, Third Edition, is a thoroughly updated and expanded new edition of a classic text in the field. Including step-by-step technical details, Volume I illustrates numerous methods for liposome preparation and auxiliary techniques necessary for the stabilization and characteriza

Liposome Technology, Volume II: Entrapment of Drugs and Other Materials into Liposomes, Third Edition is a comprehensively updated and expanded new edition of a classic text in the field. Including step-by-step technical details, Volume II describes procedures for the incorporation of drugs and other materials into liposomes for a variety therapeut

Liposome Technology, Volume III: Interactions of Liposomes with the Biological Milieu, Third Edition, is a comprehensively updated and expanded new edition of a classic text in the field. Including step-by-step technical details, Volume III describes technologies for yielding liposomes that can function in a targeted fashion, and highlights methods

Although the role of liposomes in drug targeting has been discussed extensively in several reviews and books, there has been no comprehensive coverage of related methodology. This book constitutes the first attempt to put together all aspects of lipsome technology as applied to medical sciences. Volume III is devoted to the growing variety of techniques yielding targeted liposomes and to approaches of studying liposomal behaviour in the biological milieu both in vitro and in vivo.

Although the role of liposomes in drug targeting has been discussed extensively in several reviews and books, there has been no comprehensive coverage of related methodology. This book constitutes the first attempt to put together all aspects of lipsome technology as applied to medical sciences. Volume II describes procedures for the entrapment of a number of drugs, including genetic material, into selected types of lipsomes.

Although the role of liposomes in drug targeting has been discussed extensively in several reviews and books, there has been no comprehensive coverage of related methodology. This book constitutes the first attempt to put together all aspects of lipsome technology as applied to medical sciences. Volume III is devoted to the growing variety of techniques yielding targeted liposomes and to approaches of studying liposomal behaviour in the biological milieu both in vitro and in vivo.

Although the role of liposomes in drug targeting has been discussed extensively in several reviews and books, there has been no comprehensive coverage of related methodology. This book constitutes the first attempt to put together all aspects of lipsome technology as applied to medical sciences. Volume II describes procedures for the entrapment of a number of drugs, including genetic material, into selected types of lipsomes.

Although the role of liposomes in drug targeting has been discussed extensively in several reviews and books, there has been no comprehensive coverage of related methodology. This book constitutes the first attempt to put together all aspects of lipsome technology as applied to medical sciences. Volume III is devoted to the growing variety of techniques yielding targeted liposomes and to approaches of studying liposomal behaviour in the biological milieu both in vitro and in vivo.

During the last decade or so vaccine development has been facilitated by rapid advances in molecular and cell biology. These have laid the foundations of a new generation of vaccines exemplified by subunit vaccines produced through gene cloning and by synthetic peptides mimicking small regions of proteins on the outer coat of viruses. Such peptide~ are capable of eliciting virus-neutralizing antibodies. Unfortunately, subunit and peptide vaccines are only weakly or non immunogenic in the absence of immunological adjuvants that are known to augment specific cell-mediated immune responses to the antigens and to promote the formation of protective antibodies. This book contains the proceedings of the 4th NATO Advanced Studies Institute (ASI) "Vaccines: New Generation Immunological Adjuvants" held at Cape Sounion Beach, Greece, during 24 June -5 . July 1994 and deals in depth with both theoretical and practical aspects of vaccinology. These include the role of antigen presenting cells in the induction of immune responses. immunopotentiation by a variety of new generation immunological adjuvants and vaccine carriers. and recent advances and perspectives in experimental vaccines as well as vaccinatioll with nucleic acids. We express our appreciation to Dr. K. Dalsgaard and Dr. J. L. Virelizier for their cooperatioll in planning the ASI and to Mrs. Concha Pening for her excellent production of the manuscripts. The ASI was held under the sponsorship of NATO Scientific Affairs Division and generously co-sponsored by SmithKline Beecham Pharmaceuticals (Philadelphia).

'nle NATO Advanced studies Institute series "Targeting of Drugs" was originated in 1981. It is now a major international forum, held every two years in cape Sounion, Greece, in which the present and the future of this important area of research in drug delivery is discussed in great depth. Five previous ASIs of the series dealt with drug carriers of natural and synthetic origin, their interaction with the biological milieu, with ways by which the latter influences such interaction and strategies by which milieu interference curtailing the ftmction of drug carriers is circumvented or relieved. 'nle present book contains the proceedings of the 6th NATO ASI "Targeting of Drugs: 'nle nias who, as chairperson of the Local Corrmittee, contriruted to the success of the Institute. 'nle ASI was held under the sponsorship of NATO Scientific Affairs Division and co-sponsored and generously financed by SmithKline Beecham Phannaceuticals (King of Prussia). Financial assistance was also provided by Syntex Laboratories Inc. (Palo Alto), Syntex Research (Palo Alto) and pfizer Central Research (Sandwich).

It is widely accepted that vaccination still renains the best answer to ITDst infectious diseases. Recently, vaccine developnent has been greatly facilitated by advances in ITDlecular and cell biology which have laid the foundations of a new generation of vaccines. '!hese are exemplified by submit vaccines produced through gene cloning and synthetic peptides mimicking snall regions of proteins on the outer coat of viruses and capable of eliciting virus neutralizing antibodies. However, submit and peptide vaccines are only weakly or non-inmmogenic in the absence of immunological adjuvants. The latter are a diverse array of agents that augment specific cell-mediated immune responses to the antigens and the formation of protective antibodies. '!his book contains the proceedings of the 3rd NATO Advanced Studies Institute (ASI) "New-Generation vaccines: '!he Role of Basic Irrmmology" held at Cape Sounion Beach, Greece, during 24 June-5 July, 1992.It deals with recent developnents in the understanding of inmmity at the ITDlecular and cellular levels and the application of such knowledge in the search for novel inmmological adjuvants and the fonnulation of new-generation vaccines for experimental and clinical use. We express our appreciation to Professor K. Dalsgaard and H. Snippe for their cooperation in planning the ASI and to Mrs. Concha Perring for her excellent production of the manu- scripts. '!he ASI was held tmder the sponsorship of NATO Scientific Affairs Division and generously co-sponsored by SrnithKline Beecham Pharmaceuticals (Fhiladelp,. ia). Financial assistance was also provided by Pasteur Merieux (Marcy L'Etoile), British Biotechnology Ltd.

The success of vaccination in controlling infectious diseases is well documented. However, low profitability, expense and liability have hindered research and development of vaccines. Recently, increasing realization (enhanced by the AIDS pandemic) of the need to overcome such difficulties has led to steps being taken by national authorities, non-profit and commercial organizations to resolve them. This has been facilitated by developments in recombinant DNA techniques, the advent of monoclonal anti­ bodies and progress in the understanding of the immunological structure of proteins which have laid the foundation of a new generation of vaccines. Such vaccines are defined at the molecular level, can elicit immune responses controlling infectious organisms and are therefore potentially free of the problems encountered in conventional ones. Unfortunately, subunit and synthetic peptide vaccines are often only weakly or non­ inmunogenic. However, developments in both antigen production and immuno­ potentiation of weak antigens have opened new avenues with exciting prospects for vaccine design.

TheNATO AdvancedStudiesInstituteseries"TargetingofDrugs"wasoriginatedin 1981. It is nowamajorinternationalforum,heldeverytwo yearsin CapeSounion,Greece,in whichthepresentandthefutureofthisimportantareaofresearch in drugdeliveryisdiscussed in greatdepth. PreviousASIsoftheseriesdealtwith drugcarriersofnaturalandsynthetic origin,theirinteractionswith thebiologicalmilieu, waysby whichthefunctionofdrugcarriers iscircumvented and,morerecently,with avarietyofapproaches to carrierdesignor modificationthatcontributeto optimalcarrierfunction. Thepresentbookcontainsthe proceedings ofthe8thNATO ASI, "TargetingofDrugs:Strategies for Oligonucleotideand GeneDelivery in Therapy", held in CapeSounionduring24June-5 July 1995. Asthetitle implies,thebookdealswith avarietyofsystemsin termsoftheirability to transportnucleic acidsto targetareasin vitro andin vivo in waysthateffectivelymodify,supplement, correct, orcurtailthefunctionofgenesin therapy. Weexpressourappreciation to Mrs. ConchaPerringfor herassistance with the organizationoftheASI. TheASI washeldunderthesponsorship ofNATO ScientificAffairs Division andco-sponsored andgenerouslyfinancedby SmithKlineBeechamPharmaceuticals (KingofPrussia).Financialassistance wasalsoprovidedby SandozPharma(Baseland Athens),GeneMedicine (Houston,USA), ChironCorporation(Emeryville,USA), BYK GuldenLombergChemische (Konstanz,Gernlany),HelpSA(Athens,Greece),Avanti Polar Lipids Inc (Birmingham,USA), OxfordMolecular(Oxford,UK), Pfizer(Kent,UK), andAlza Corporation(PaloAlto, USA). GregoryGregoriadis BrendaMcCormack v CONTENTS Gene Therapy for Inherited Genetic Disease: Possibilities and Problems c. *Coutelle Gene Delivery and Therapy: The Case for Cystic Fibrosis 15 E. W. F. W. Alton Immune Responses with Direct Gene Transfer: DNA Vaccines and 21 Implications for Gene Therapy H. L. Davis Oligonucleotides: Molecular Versions for Optimal Use in Vivo 31 E. Saison-Behmoaras, A. Van Aerschot, I. Duroux, C. Hendrix, C. Helene, and P. Herdewijn Retrovirus Vectors in Gene Therapy: Targeting to Specific Cells 45 AJ. Kingsman, Y. Bae, J. c. Griffiths, N. Kim, E. E. Ramsdale, G. Romano, Y. Soneoka, P. M. Cannon, and S. M. Kingsman Adenovirus as Vectors for Gene Therapy 53 M. G. Lee Receptor-Mediated Gene Delivery with Synthetic Virus-like Particles 67 E. Wagner, M. Cotten, and K.Zatloukal Controllable Gene Therapy: Recent Advances in Non-Viral Gene Delivery 79 A.

During the last decade or so vaccine development has been facilitated by rapid advances in molecular and cell biology. These have laid the foundations of a new generation of vaccines exemplified by subunit vaccines produced through gene cloning and by synthetic peptides mimicking small regions of proteins on the outer coat of viruses. Such peptide~ are capable of eliciting virus-neutralizing antibodies. Unfortunately, subunit and peptide vaccines are only weakly or non immunogenic in the absence of immunological adjuvants that are known to augment specific cell-mediated immune responses to the antigens and to promote the formation of protective antibodies. This book contains the proceedings of the 4th NATO Advanced Studies Institute (ASI) "Vaccines: New Generation Immunological Adjuvants" held at Cape Sounion Beach, Greece, during 24 June -5 . July 1994 and deals in depth with both theoretical and practical aspects of vaccinology. These include the role of antigen presenting cells in the induction of immune responses. immunopotentiation by a variety of new generation immunological adjuvants and vaccine carriers. and recent advances and perspectives in experimental vaccines as well as vaccinatioll with nucleic acids. We express our appreciation to Dr. K. Dalsgaard and Dr. J. L. Virelizier for their cooperatioll in planning the ASI and to Mrs. Concha Pening for her excellent production of the manuscripts. The ASI was held under the sponsorship of NATO Scientific Affairs Division and generously co-sponsored by SmithKline Beecham Pharmaceuticals (Philadelphia).