Feb 11, Gene Therapy. Sam K.P. Kung Immunology Rm 417 Apotex Center
|
|
- Christina King
- 5 years ago
- Views:
Transcription
1 Gene Therapy Sam K.P. Kung Immunology Rm 417 Apotex Center
2 Objectives: The concept of gene therapy, and an introduction of some of the currently used gene therapy vector Undesirable immune responses to gene therapy approach Potential gene therapy approach in modulating immune responses Examples of applications
3 It is an approach to treating disease by either modifying the expressions of an individual's genes or correction of abnormal genes. By administration of DNA rather than a drug, many different diseases are currently being investigated as candidates for gene therapy. These include cystic fibrosis, cardiovascular disease, infectious diseases such as AIDS and cancer. Cell Therapy can be defined as the infusion or transplantation of whole cells into a patient for the treatment of an inherited or acquired disease
4 Why do we need it? Feb 11, 2013
5 What do we need to do this? Administration Delivery system Efficiency and efficacy Target Gene X Therapeutic gene Safe
6 Gene Therapy Choice of vector in gene therapy application is important = Pathogens?
7 Limitations that hampered the progress gene delivery Inefficient Specific targeting of expression to the cells or tissues of interest only. Duration of expression Safety Immune responses
8 An ideal gene therapy vector Allow efficient and selective transduction of the target cells The vector is maintained inside the cells Expresses gene of interest at levels necessary for achieving therapeutic effects Safe
9 Gene Transfer Technology Non-viral (chemical, liposome, electroporation of DNA) Viral (gene transfer vector derived from virus)
10 Currently used gene therapy viral vectors Adenovirus Adeno-associated virus Alphaviruses Herpes Simplex Virus Retrovirus Lentivirus
11 Viral vectors used for gene delivery Feb 11, 2013
12 Viral vectors used for gene delivery Feb 11, 2013
13 Adenovirus Linear double-stranded DNA Genome size is ~ 35 kb Nonenveloped Transcription proceeds according to a carefully orchestrated program, with viral genes being transcribed early after infection, and others being transcribed at later times
14 Adenovirus Pros High titer virus stock is possible High level of gene expression Cons Preexisting immunity to the virus Strong immunogenicity Transient expression, no genome integration
15 Retrovirus The viral genome is a dimer of linear, positive-sense, single-stranded RNA Genome size is ~7-13 kb Require reverse transcription for replication and integration The genome contains three large genes, gag (group-specific antigen), Pol (polymerase) and env (envelope) Eg. Moloney Murine leukemia virus
16 Retrovirus Pros Long-term expression possible, genome integration Ability to pseudotype with other viral envelope proteins to Increase Target range Cons Inability to infect non-dividing cells Sites of Integration
17 Lentivirus The viral genome is a dimer of linear, positive-sense, single-stranded RNA Genome size is ~10 kb Require reverse transcription for replication and integration The genome contains three large genes, gag, Pol (polymerase) and env (envelope). In addition, six additional viral proteins Are the primary translation products of spliced mrna Eg. HIV-1
18 Lentivirus Human Immunodeficiency virus Pathogenesis/Clinical Significance Acquired Immunodeficiency Syndrome HIV envelope binds CD4 molecule (T helper cells) Transmission routes: sexual contact, blood, breast feeding So far, non-oncogenic
19 Lentivirus Pros Ability to infect both dividing and non-dividing cells Long-term expression possible, genome integration Ability to pseudotype with other viral envelope proteins to increase Target range Cons Safety concerns Sites of Integration
20 Major Success Story Retrovirus-based treatment of infants suffering from the X- chromosome-linked severe combined immunodeficiency disease (SCID) (bubble children). Following this treatment, these children have been able to live in the open air.
21 Figure 2 Longitudinal study of lymphocyte subsets from patient 1 (P1) and patient 2 (P2). M Cavazzana-Calvo et al. Science 2000;288: Published by AAAS
22 Updates (as of 2012) Feb 11, 2013
23 Discussion Feb 11, 2013
24 Choice of vectors in gene therapy applications is important Feb 11, 2013
25 Adenovirus Experience Feb 11, 2013
26 Adenoviruses Double-stranded DNA virus genome ~34 43 kb Species specific and of different serotypes 51 serotypes in humans 27 serotypes in simian 7 chimpanzees
27 Adenoviral vectors attractive candidate gene replacement vehicles Genome is well characterized and relatively easy to manipulate Adenoviruses cause mild diseases in immunocompetent human adults. Can be made replication-defective by deletions of crucial viral proteins Broad tropism infecting a variety of dividing and non-dividing cells High titers in culture
28 Adenoviral vectors attractive candidate gene replacement vehicles An example: Ornithine transcarbamylase deficiency
29 Ornithine Transcarbamylase Deficiency X-linked disorder resulting in a deficiency of the OTC enzyme, that leads to marked elevations of ammonia. Liver is the main target organ Animal models available in mice Current treatment: diet, sodium benzoate
30 2x10 11 vectors Tail vein injections into OTC deficient mice (spf, ash) Blood sampling
31 Urinary orotate excretion in OTC-deficient mice infused with adenoviral vectors carrying mouse OTC cdna Feb 11, 2013
32 Summary: Molecular Genetics and Metabolis 80 (2003), An 18-year-old male with partial ornithine transcarbmaylase (OTC) deficiency participated in a pilot (safety) study of gene therapy. The vectors were infused into the right hepatic artery at a dose of 6x1011 particles/kg. 98 h following gene transfer, he was dead. The subject had high serum levels of IL-6 and IL-10 but normal TNF immediately after infusion of the vector. This experience points to the limitations of animal studies in predicting human responses, the steep toxicity curve for replication defective adenovirus vectors, substantial subject-to-subject variation in host responses to systemically administered vectors, and the need for further study of the immune response to these vectors.
33 Molecular Therapy, 3:697 (2001) C57BL6 mice were injected intravenously with Ad-lacZ sacrificed at the indicated time points. Heart blood was taken for cytokine assays Spleen was harvested for culture of DCs and macrophages and used for immunohistochemical and X-gal staining.
34 Intravenous injection of mice with Ad-lacZ significantly induces elevation of serum inflammatory cytokines. Feb 11, 2013
35 Bangari and Mittal, Curr Gene Ther : Feb 11, 2013
36 Bangari and Mittal, Curr Gene Ther : Feb 11, 2013
37 Summary of the Adenovirus Experience Immediate hypersensitivity to adenovirus, which results in increased release of TNF-, IL-6 and IL-8 can have lethal consequences (toxicity). Cellular responses may develop and destroy successfully transduced cells or reduce transgene expression (limit transduction efficiency) Preexisting humoral immunity to vectors or development of antibodies against transgene product or vector components (limit transduction efficiency)
38 Approaches to avoid immune system Further Deletion of viral genes Ehrhardt et al., A gene-deleted adenoviral vector results in phenotypic correction of canine hemophilia B without liver toxicity or thrombocytopenia. Blood 102: (2003). Immunosuppression Ziller et al., Transient blocking of both B7.1 (CD80) and B7.2 (CD86) in addition to CD40- CD40L interaction fully abrogates the immune response following systemic injection of adenovirus vector. Gene Therapy 9: (2002). Switching serotypes Kass-Eisler et al., Circumventing the immune response to adenovirus-mediated gene therapy. Gene Ther. 3(2): (1996)
39 Approach to take advantage of the immune system Adenoviral vectors attractive vaccine vehicles
40 Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity Shiver et al., Nature 415:331 (2002) Non-human primate SHIV-89.6P challenge CD4 counts and viral load
41 Figure 2 Post-challenge viraemia and CD4+ T-cell counts. Feb 11, 2013
42 Figure 1 Quantification of CD8+ T-cell responses by tetramer analysis during immunization. Feb 11, 2013
43 CD8 Feb 11, 2013 IFN-
44 HIV-1 based lentiviral vectors HIV-1 LTR gag vif vpr vpu tat rev LTR pol env nef HR CMVEGFP LTR CMV EGFP LTR
45 Key differences between retroviral and lentiviral vectors Cell-cycle requirements for successful transduction Preference in the Integration sites Vector silencing?
46 Manufacture of lentiviral vectors LTR CMV CMV CMV EGFP env + gag pol + LTR Gene Therapy Vector Packaging Vector Envelope Vector CaPO 4 transfection 293T cells Harvest Virus Supernatant
47 CD4 Feb 11, 2013 CS-RhMLV-E in vitro U3 R U5 Rh-MLV LTR EGFP U3 R U5 gag MoMLV CS-RhMLV-E CS-RhMLV-E CSCG Activated Human T cells EGFP Kung et al., J. Virol. 74:
48 Transplantation of transduced CD34+ cells in rhesus macaques GCSF SCF Peripheral Blood CD34+ cells 10 Gy FACS PBMC In vitro Lentiviral Transduction
49 Lentiviral vector marking of rhesus peripheral blood cells Granulocytes Monocytes Lymphocytes RBC Platelet CS-RhMLV-E HR CMVEGFP EGFP An and Kung et al., J. Virol. 75:
50 CD34 Feb 11, 2013 EGFP markings in rhesus bone marrow aspirates CS-RhMLV-E 95E132 HR CMVEGFP RC505 EGFP
51
52
53
54
55
56
57 New Designs Cell-specific targeting Non-integrating Lentiviral vectors mirna-regulated Lentiviral vectors
58 Morizono et al., J Virol Sep;75(17): Feb 11, 2013
59 Morizono et al., Nat Med Mar;11(3): Feb 11, 2013
60 Morizono et al., Nat Med Mar;11(3): Feb 11, 2013
61 Genetic engineering of T cells for adoptive immunotherapy Feb 11, 2013
62
63
64
65
66
67
68 HSC-based gene therapy approaches to treat HIV infection Kitchen S.G., et al., Virology 2011
69 Inhibitory agents used in HIV hematopoietic cell gene therapy trials Feb 11, 2013
70
71
72 Take Home Messages Gene therapy as a modern therapeutic for both hereditary and acquired diseases. The progress has been slower than anticipated because of the Setbacks and the major limitations on vector developments No universally applicable viral vector system is ideal for all clinical applications. Because of the various properties of each viral vector, the choice of a vector depends on factors such as packaging capacity, host range, cellor tissue-specific targeting, genome integration and duration of transgene expression.
73 Take home message SCIDs provide conditions that favor successful outcomes following gene therapy -stable integration of vector -selection pressure -lack of immune responses -in SCID-X1, no concern about unwanted ectopic expression, and de-regulated cell activation SCID-X1 treatments presented proof of principle for gene therapy clinically The use of retrovirus (and lentivirus) raises concern of insertational mutagenesis Limitations in animal models Need to improve vector designs and site-specific integration
74 Take home message Things to consider in designing a gene therapy protocol Host immunity presents a challenge to the simple rationale behind metabolic gene replacement therapy: supply the missing gene and cure the disease. Need to seriously consider making immunomodulation as important a part as are vectors and transgenes. Host immunity against certain viral vectors can be useful in vaccine designs. Ability to manipulate primary cells of hematopoietic lineages also allow direct genetic manipulation of immune responses.
VIROLOGY. Engineering Viral Genomes: Retrovirus Vectors
VIROLOGY Engineering Viral Genomes: Retrovirus Vectors Viral vectors Retrovirus replicative cycle Most mammalian retroviruses use trna PRO, trna Lys3, trna Lys1,2 The partially unfolded trna is annealed
More informationViral Vectors In The Research Laboratory: Just How Safe Are They? Dawn P. Wooley, Ph.D., SM(NRM), RBP, CBSP
Viral Vectors In The Research Laboratory: Just How Safe Are They? Dawn P. Wooley, Ph.D., SM(NRM), RBP, CBSP 1 Learning Objectives Recognize hazards associated with viral vectors in research and animal
More informationRecombinant Protein Expression Retroviral system
Recombinant Protein Expression Retroviral system Viruses Contains genome DNA or RNA Genome encased in a protein coat or capsid. Some viruses have membrane covering protein coat enveloped virus Ø Essential
More informationFayth K. Yoshimura, Ph.D. September 7, of 7 RETROVIRUSES. 2. HTLV-II causes hairy T-cell leukemia
1 of 7 I. Diseases Caused by Retroviruses RETROVIRUSES A. Human retroviruses that cause cancers 1. HTLV-I causes adult T-cell leukemia and tropical spastic paraparesis 2. HTLV-II causes hairy T-cell leukemia
More informationOCCUPATIONAL HEALTH CONSIDERATIONS FOR WORK WITH VIRAL VECTORS
OCCUPATIONAL HEALTH CONSIDERATIONS FOR WORK WITH VIRAL VECTORS GARY R. FUJIMOTO, M.D. PALO ALTO MEDICAL FOUNDATION ADJUNCT ASSOCIATE CLINICAL PROFESSOR OF MEDICINE DIVISION OF INFECTIOUS DISEASES AND GEOGRAPHIC
More informationFayth K. Yoshimura, Ph.D. September 7, of 7 HIV - BASIC PROPERTIES
1 of 7 I. Viral Origin. A. Retrovirus - animal lentiviruses. HIV - BASIC PROPERTIES 1. HIV is a member of the Retrovirus family and more specifically it is a member of the Lentivirus genus of this family.
More informationRetroviruses. ---The name retrovirus comes from the enzyme, reverse transcriptase.
Retroviruses ---The name retrovirus comes from the enzyme, reverse transcriptase. ---Reverse transcriptase (RT) converts the RNA genome present in the virus particle into DNA. ---RT discovered in 1970.
More information~Lentivirus production~
~Lentivirus production~ May 30, 2008 RNAi core R&D group member Lentivirus Production Session Lentivirus!!! Is it health threatening to lab technician? What s so good about this RNAi library? How to produce
More informationVIRUSES AND CANCER Michael Lea
VIRUSES AND CANCER 2010 Michael Lea VIRAL ONCOLOGY - LECTURE OUTLINE 1. Historical Review 2. Viruses Associated with Cancer 3. RNA Tumor Viruses 4. DNA Tumor Viruses HISTORICAL REVIEW Historical Review
More informationHIV INFECTION: An Overview
HIV INFECTION: An Overview UNIVERSITY OF PAPUA NEW GUINEA SCHOOL OF MEDICINE AND HEALTH SCIENCES DIVISION OF BASIC MEDICAL SCIENCES DISCIPLINE OF BIOCHEMISTRY & MOLECULAR BIOLOGY PBL MBBS II SEMINAR VJ
More informationChoosing Between Lentivirus and Adeno-associated Virus For DNA Delivery
Choosing Between Lentivirus and Adeno-associated Virus For DNA Delivery Presenter: April 12, 2017 Ed Davis, Ph.D. Senior Application Scientist GeneCopoeia, Inc. Outline Introduction to GeneCopoeia Lentiviral
More informationHuman Immunodeficiency Virus
Human Immunodeficiency Virus Virion Genome Genes and proteins Viruses and hosts Diseases Distinctive characteristics Viruses and hosts Lentivirus from Latin lentis (slow), for slow progression of disease
More informationA phase I pilot study of safety and feasibility of stem cell therapy for AIDS lymphoma using stem cells treated with a lentivirus vector encoding
A phase I pilot study of safety and feasibility of stem cell therapy for AIDS lymphoma using stem cells treated with a lentivirus vector encoding multiple anti-hiv RNAs John A. Zaia, M.D. John J. Rossi,
More informationA Novel Recombinant Virus Reagent Products for Efficient Preparation Of Hepatitis B Animal Models
About FivePlus Beijing FivePlus Molecular Medicine Institute was established in 2005. The company has been dedicating itself to continuous innovation of viral vectors. The meaning of FivePlus is based
More informationHIV & AIDS: Overview
HIV & AIDS: Overview UNIVERSITY OF PAPUA NEW GUINEA SCHOOL OF MEDICINE AND HEALTH SCIENCES DIVISION OF BASIC MEDICAL SCIENCES DISCIPLINE OF BIOCHEMISTRY & MOLECULAR BIOLOGY PBL SEMINAR VJ TEMPLE 1 What
More informationChoosing Optimal Viral Vector for T-cell Transduction. Viral vectors for blood cells
Choosing Optimal Viral Vector for T-cell Transduction Max Mamonkin, PhD Center for Cell and Gene Therapy Baylor College of Medicine PACT Webinar Nov 08, 2018 Viral for blood cells Short/long term gene
More informationExperimental Therapeutics I
Experimental Therapeutics I Mary Hitt 5142 Katz Group Centre mhitt@ualberta.ca; or Mary.Hitt@albertahealthservices.ca 1 Specific Topics for Today Preclinical and clinical testing Gene therapy Nonviral
More informationB19, see Parvovirus B19 Bone marrow, gene transfer with parvovirus. Erythrovirus, see Parvovirus B19, Simian parvovirus
... Subject Index Adeno-associated virus Cap and genome encapsidation 87 DNA integration homologous recombination 90, 91 latency vs replication 77, 78 mechanism 79 requirements 78, 79 site in human genome
More informationCurrent Strategies in HIV-1 Vaccine Development Using Replication-Defective Adenovirus as a Case Study
Note: I have added some clarifying comments to the slides -- please click on Comments under View to see them. Current Strategies in HIV-1 Vaccine Development Using Replication-Defective Adenovirus as a
More informationViral vectors. Part I. 27th October 2014
Viral vectors Part I 27th October 2014 Prof. Józef Dulak, PhD, DSc Department of Medical Biotechnology Faculty of Biochemistry, Biophysics and Biotechnology Room 3.025/3.07 Phone 664-63-75 Email: jozef.dulak@uj.edu.pl
More informationOncolytic Immunotherapy: A Local and Systemic Antitumor Approach
Oncolytic Immunotherapy: A Local and Systemic Antitumor Approach Oncolytic immunotherapy Oncolytic immunotherapy the use of a genetically modified virus to attack tumors and induce a systemic immune response
More informationReview and Public RAC Discussion of Protocol #
Review and Public RAC Discussion of Protocol #0508 725 A phase I pilot study of safety and feasibility of stem cell therapy for AIDS lymphoma using stem cells treated with a lentivirus vector encoding
More informationVIRUSES. 1. Describe the structure of a virus by completing the following chart.
AP BIOLOGY MOLECULAR GENETICS ACTIVITY #3 NAME DATE HOUR VIRUSES 1. Describe the structure of a virus by completing the following chart. Viral Part Description of Part 2. Some viruses have an envelope
More informationProkaryotic Biology. VIRAL STDs, HIV-1 AND AIDS
Prokaryotic Biology VIRAL STDs, HIV-1 AND AIDS Prokaryotic Biology FROM THE CDC VIRAL STDs, HIV-1 AND AIDS VIRAL STDs & CONTACT VIRAL DISEASES A. GENITAL HERPES & COLD SORES 1. HERPES SIMPLEX VIRUS-2 (HHV-2)
More informationHuman Immunodeficiency Virus. Acquired Immune Deficiency Syndrome AIDS
Human Immunodeficiency Virus Acquired Immune Deficiency Syndrome AIDS Sudden outbreak in USA of opportunistic infections and cancers in young men in 1981 Pneumocystis carinii pneumonia (PCP), Kaposi s
More information1. Virus 2. Capsid 3. Envelope
VIRUSES BIOLOGY II VOCABULARY- VIRUSES (22 Words) 1. Virus 2. Capsid 3. Envelope 4. Provirus 5. Retrovirus 6. Reverse transcriptase 7. Bacteriophage 8. Lytic Cycle 9. Virulent 10. Lysis 11. Lysogenic Cycle
More informationIntroduction retroposon
17.1 - Introduction A retrovirus is an RNA virus able to convert its sequence into DNA by reverse transcription A retroposon (retrotransposon) is a transposon that mobilizes via an RNA form; the DNA element
More informationGene Therapies. Josh Crockett, Lexi Trujillo, Caitlin Halliday
Gene Therapies Josh Crockett, Lexi Trujillo, Caitlin Halliday Gene Therapy Main objective: create carriers that can envelope and deliver genetic materials into target tissues (like cancerous cells) in
More informationReplication competent lentivirus (RCL) and replication competent retrovirus (RCR) testing of drug product. Kenneth Cornetta MD Indiana University
Replication competent lentivirus (RCL) and replication competent retrovirus (RCR) testing of drug product Kenneth Cornetta MD Indiana University Outline Risk from Exposure Risk of Exposure Clinical findings
More informationCURRENT DEVELOMENTS AND FUTURE PROSPECTS FOR HIV GENE THERAPY USING INTERFERING RNA-BASED STRATEGIES
[Frontiers in Bioscience 5, d527-555, May 1, 2000] CURRENT DEVELOMENTS AND FUTURE PROSPECTS FOR HIV GENE THERAPY USING INTERFERING RNA-BASED STRATEGIES Betty Lamothe, Sadhna Joshi Department of Medical
More informationUnder the Radar Screen: How Bugs Trick Our Immune Defenses
Under the Radar Screen: How Bugs Trick Our Immune Defenses Session 7: Cytokines Marie-Eve Paquet and Gijsbert Grotenbreg Whitehead Institute for Biomedical Research HHV-8 Discovered in the 1980 s at the
More informationThis training module is required for all personnel listed on an IBC protocol that describes work utilizing viral vectors (both replication competent
This training module is required for all personnel listed on an IBC protocol that describes work utilizing viral vectors (both replication competent and incompetent) regardless of the biosafety level used
More informationDynamics of lentiviral infection in vivo in the absence of adaptive immune responses
Dynamics of lentiviral infection in vivo in the absence of adaptive immune responses Elissa J. Schwartz Associate Professor School of Biological Sciences Department of Mathematics & Statistics Washington
More informationRAISON D ETRE OF THE IMMUNE SYSTEM:
RAISON D ETRE OF THE IMMUNE SYSTEM: To Distinguish Self from Non-Self Thereby Protecting Us From Our Hostile Environment. Innate Immunity Acquired Immunity Innate immunity: (Antigen nonspecific) defense
More informationGENE THERAPY: Twenty-First Century Medicine
Annu. Rev. Biochem. 2005. 74:711 38 doi: 10.1146/annurev.biochem.74.050304.091637 Copyright c 2005 by Annual Reviews. All rights reserved First published online as a Review in Advance on March 11, 2005
More informationFig. 1: Schematic diagram of basic structure of HIV
UNIVERSITY OF PAPUA NEW GUINEA SCHOOL OF MEDICINE AND HEALTH SCIENCES DIVISION OF BASIC MEDICAL SCIENCES DISCIPLINE OF BIOCHEMISTRY & MOLECULAR BIOLOGY PBL SEMINAR HIV & AIDS: An Overview What is HIV?
More informationCDC site UNAIDS Aids Knowledge Base http://www.cdc.gov/hiv/dhap.htm http://hivinsite.ucsf.edu/insite.jsp?page=kb National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/default.htm
More informationHow HIV Causes Disease Prof. Bruce D. Walker
How HIV Causes Disease Howard Hughes Medical Institute Massachusetts General Hospital Harvard Medical School 1 The global AIDS crisis 60 million infections 20 million deaths 2 3 The screen versions of
More informationHIV Immunopathogenesis. Modeling the Immune System May 2, 2007
HIV Immunopathogenesis Modeling the Immune System May 2, 2007 Question 1 : Explain how HIV infects the host Zafer Iscan Yuanjian Wang Zufferey Abhishek Garg How does HIV infect the host? HIV infection
More informationMedChem 401~ Retroviridae. Retroviridae
MedChem 401~ Retroviridae Retroviruses plus-sense RNA genome (!8-10 kb) protein capsid lipid envelop envelope glycoproteins reverse transcriptase enzyme integrase enzyme protease enzyme Retroviridae The
More informationScreening for Complex Phenotypes
Screening for Complex Phenotypes Michael Hemann hemann@mit.edu Screening for cancer phenotypes in mice How do we typically model cancer in mice? Tumor Suppressor KO Oncogene transgenesis Problems with
More informationImmunity and Infection. Chapter 17
Immunity and Infection Chapter 17 The Chain of Infection Transmitted through a chain of infection (six links) Pathogen: Disease causing microorganism Reservoir: Natural environment of the pathogen Portal
More informationSupporting Information
Supporting Information Sui et al..7/pnas.997 Pre-CLP CM9 LA9 SL Tat# Pol Vif % Tetramer + CD + CD + Vac+IL- +IL- Vac Fig. S. Frequencies of six different CD + CD + Mamu-A*-tetramer + cells were measured
More informationGene Therapy for Sickle Cell Disease: A Safety/Efficacy Trial
Gene Therapy for Sickle Cell Disease: A Safety/Efficacy Trial Elizabeth Hexner A. Introduction Sickle cell disease (SCD) is an autosomal recessive disease of red blood cells (RBCs). A single amino acid
More informationLentiviral and Retroviral Vector Systems
3 Lentiviral and Retroviral Vector Systems Renata Stripecke, PhD and Noriyuki Kasahara, MD, PhD CONTENTS INTRODUCTION BASIC PRINCIPLES OF RETROVIRAL VECTOR TECHNOLOGY APPLICATIONS OF RETROVIRAL GENE TRANSFER
More informationFebruary 14, 2003 Report on preclinical studies in gc-ko mice Fabio Candotti
February 14, 2003 Report on preclinical studies in gc-ko mice Fabio Candotti Five published reports (see details below) have described the development of peripheral blood lymphocytes as well as cellular
More informationVirology Introduction. Definitions. Introduction. Structure of virus. Virus transmission. Classification of virus. DNA Virus. RNA Virus. Treatment.
DEVH Virology Introduction Definitions. Introduction. Structure of virus. Virus transmission. Classification of virus. DNA Virus. RNA Virus. Treatment. Definitions Virology: The science which study the
More informationJulianne Edwards. Retroviruses. Spring 2010
Retroviruses Spring 2010 A retrovirus can simply be referred to as an infectious particle which replicates backwards even though there are many different types of retroviruses. More specifically, a retrovirus
More informationModule 2 In vivo gene therapy. Lecture 7. In-situ, in-vivo and ex-vivo gene therapy (part I)
Module 2 In vivo gene therapy Lecture 7 In-situ, in-vivo and ex-vivo gene therapy (part I) Somatic cell gene therapy involves the transfer of gene to a diseased somatic cell either within the body or outside
More informationRunning Head: AN UNDERSTANDING OF HIV- 1, SYMPTOMS, AND TREATMENTS. An Understanding of HIV- 1, Symptoms, and Treatments.
Running Head: AN UNDERSTANDING OF HIV- 1, SYMPTOMS, AND TREATMENTS An Understanding of HIV- 1, Symptoms, and Treatments Benjamin Mills Abstract HIV- 1 is a virus that has had major impacts worldwide. Numerous
More informationHIV/AIDS. Biology of HIV. Research Feature. Related Links. See Also
6/1/2011 Biology of HIV Biology of HIV HIV belongs to a class of viruses known as retroviruses. Retroviruses are viruses that contain RNA (ribonucleic acid) as their genetic material. After infecting a
More informationNK mediated Antibody Dependent Cellular Cytotoxicity in HIV infections
NK mediated Antibody Dependent Cellular Cytotoxicity in HIV infections Amy Chung Dr. Ivan Stratov Prof. Stephen Kent ADCC process consists of Target cell QuickTime and a TIFF (Uncompressed) FcγR decompressor
More informationRAISON D ETRE OF THE IMMUNE SYSTEM:
RAISON D ETRE OF THE IMMUNE SYSTEM: To Distinguish Self from Non-Self Thereby Protecting Us From Our Hostile Environment. Innate Immunity Adaptive Immunity Innate immunity: (Antigen - nonspecific) defense
More informationVersion A. AP* Biology: Immune System. Name: Period
Name: Period Version A AP* Biology: Immune System Directions: Each of the questions or incomplete statements below is followed by four suggested answers or completions. Select the one that is best in each
More informationCenters for Disease Control August 9, 2004
HIV CDC site UNAIDS Aids Knowledge Base http://www.cdc.gov/hiv/dhap.htm http://hivinsite.ucsf.edu/insite.jsp?page=kb National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/default.htm
More informationBIT 120. Copy of Cancer/HIV Lecture
BIT 120 Copy of Cancer/HIV Lecture Cancer DEFINITION Any abnormal growth of cells that has malignant potential i.e.. Leukemia Uncontrolled mitosis in WBC Genetic disease caused by an accumulation of mutations
More informationDNA Vaccines against Human Immunodeficiency Virus Type 1 in the Past Decade
CLINICAL MICROBIOLOGY REVIEWS, Apr. 2004, p. 370 389 Vol. 17, No. 2 0893-8512/04/$08.00 0 DOI: 10.1128/CMR.17.2.370 389.2004 Copyright 2004, American Society for Microbiology. All Rights Reserved. DNA
More informationA PROJECT ON HIV INTRODUCED BY. Abdul Wahab Ali Gabeen Mahmoud Kamal Singer
A PROJECT ON HIV INTRODUCED BY Abdul Wahab Ali Gabeen Mahmoud Kamal Singer Introduction: Three groups of nations have been identified in which the epidemiology of HIV(Human Immunodeficiency Virus) varies:
More informationLecture 11. Immunology and disease: parasite antigenic diversity
Lecture 11 Immunology and disease: parasite antigenic diversity RNAi interference video and tutorial (you are responsible for this material, so check it out.) http://www.pbs.org/wgbh/nova/sciencenow/3210/02.html
More informationRecombinant adeno-associated virus vectors induce functionally impaired transgene product specific CD8 + T cells in mice
Recombinant adeno-associated virus vectors induce functionally impaired transgene product specific CD8 + T cells in mice Shih-Wen Lin,, Marcio O. Lasaro, Hildegund C.J. Ertl J Clin Invest. 2007;117(12):3958-3970.
More informationLecture 2: Virology. I. Background
Lecture 2: Virology I. Background A. Properties 1. Simple biological systems a. Aggregates of nucleic acids and protein 2. Non-living a. Cannot reproduce or carry out metabolic activities outside of a
More informationJumpstart your research with ViraPower Lentiviral Expression Systems
ViraPower Lentiviral Expression Systems Jumpstart your research with ViraPower Lentiviral Expression Systems With ViraPower Lentiviral Systems you can: Efficiently transduce both dividing and non-dividing
More informationSection Lectures: Immunology/Virology Time: 9:00 am 10:00 am LRC 105 A & B
Section Director: Cliff Bellone, Ph.D. Office: Doisy Hall - R 405 Phone: 577-8449 E-Mail: bellonec@slu.edu Lecturers: James Swierkosz, Ph.D. Office: Medical School Rm. 412 Phone: 577-8430 E-Mail: swierkoszje@slu.edu
More informationEffective activity of cytokine-induced killer cells against autologous metastatic melanoma including cells with stemness features
Effective activity of cytokine-induced killer cells against autologous metastatic melanoma including cells with stemness features Loretta Gammaitoni, Lidia Giraudo, Valeria Leuci, et al. Clin Cancer Res
More informationTranscription and RNA processing
Transcription and RNA processing Lecture 7 Biology W3310/4310 Virology Spring 2016 It is possible that Nature invented DNA for the purpose of achieving regulation at the transcriptional rather than at
More informationSupplementary information. MARCH8 inhibits HIV-1 infection by reducing virion incorporation of envelope glycoproteins
Supplementary information inhibits HIV-1 infection by reducing virion incorporation of envelope glycoproteins Takuya Tada, Yanzhao Zhang, Takayoshi Koyama, Minoru Tobiume, Yasuko Tsunetsugu-Yokota, Shoji
More information7.012 Quiz 3 Answers
MIT Biology Department 7.012: Introductory Biology - Fall 2004 Instructors: Professor Eric Lander, Professor Robert A. Weinberg, Dr. Claudette Gardel Friday 11/12/04 7.012 Quiz 3 Answers A > 85 B 72-84
More informationImmunodeficiencies HIV/AIDS
Immunodeficiencies HIV/AIDS Immunodeficiencies Due to impaired function of one or more components of the immune or inflammatory responses. Problem may be with: B cells T cells phagocytes or complement
More informationTranscription and RNA processing
Transcription and RNA processing Lecture 7 Biology 3310/4310 Virology Spring 2018 It is possible that Nature invented DNA for the purpose of achieving regulation at the transcriptional rather than at the
More information08/02/59. Tumor Immunotherapy. Development of Tumor Vaccines. Types of Tumor Vaccines. Immunotherapy w/ Cytokine Gene-Transfected Tumor Cells
Tumor Immunotherapy Autologous virus Inactivation Inactivated virus Lymphopheresis Culture? Monocyte s Dendritic cells Immunization Autologous vaccine Development of Tumor Vaccines Types of Tumor Vaccines
More informationNucleic acid: singled stranded, double stranded, RNA, or DNA, linear or circular. Capsid: protein coat that is most of the mass of the virus.
Viruses General Characteristics of Viruses 1. Depending on view may be regarded as exceptionally complex aggregates of nonliving chemicals or as exceptionally simple living microbes. 2. Contain a single
More informationFostering Clinical Development for HIV-1 Vaccine
W Fostering Clinical Development for HIV-1 Vaccine Ravimiarenduse alane seminar 9. oktoobril Tallinnas Mart Ustav, PhD CSO, SVP 1 FIT Biotech Founded in 1995 Operations in Tampere, Finland and Tartu, Estonia
More informationCOURSE: Medical Microbiology, PAMB 650/720 - Fall 2008 Lecture 16
COURSE: Medical Microbiology, PAMB 650/720 - Fall 2008 Lecture 16 Tumor Immunology M. Nagarkatti Teaching Objectives: Introduction to Cancer Immunology Know the antigens expressed by cancer cells Understand
More information7.012 Problem Set 6 Solutions
Name Section 7.012 Problem Set 6 Solutions Question 1 The viral family Orthomyxoviridae contains the influenza A, B and C viruses. These viruses have a (-)ss RNA genome surrounded by a capsid composed
More informationLESSON 4.6 WORKBOOK. Designing an antiviral drug The challenge of HIV
LESSON 4.6 WORKBOOK Designing an antiviral drug The challenge of HIV In the last two lessons we discussed the how the viral life cycle causes host cell damage. But is there anything we can do to prevent
More informationCytokines modulate the functional activities of individual cells and tissues both under normal and pathologic conditions Interleukins,
Cytokines http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter22/animation the_immune_response.html Cytokines modulate the functional activities of individual cells and tissues both under
More informationDEBATE ON HIV ENVELOPE AS A T CELL IMMUNOGEN HAS BEEN GAG-GED
DEBATE ON HIV ENVELOPE AS A T CELL IMMUNOGEN HAS BEEN GAG-GED Viv Peut Kent Laboratory, University of Melbourne, Australia WHY ENVELOPE? Env subject to both humoral and cellular immune responses Perhaps
More informationGenome of Hepatitis B Virus. VIRAL ONCOGENE Dr. Yahwardiah Siregar, PhD Dr. Sry Suryani Widjaja, Mkes Biochemistry Department
Genome of Hepatitis B Virus VIRAL ONCOGENE Dr. Yahwardiah Siregar, PhD Dr. Sry Suryani Widjaja, Mkes Biochemistry Department Proto Oncogen and Oncogen Oncogen Proteins that possess the ability to cause
More informationSupplemental Materials and Methods Plasmids and viruses Quantitative Reverse Transcription PCR Generation of molecular standard for quantitative PCR
Supplemental Materials and Methods Plasmids and viruses To generate pseudotyped viruses, the previously described recombinant plasmids pnl4-3-δnef-gfp or pnl4-3-δ6-drgfp and a vector expressing HIV-1 X4
More informationDATA SHEET. Provided: 500 µl of 5.6 mm Tris HCl, 4.4 mm Tris base, 0.05% sodium azide 0.1 mm EDTA, 5 mg/liter calf thymus DNA.
Viral Load DNA >> Standard PCR standard 0 Copies Catalog Number: 1122 Lot Number: 150298 Release Category: A Provided: 500 µl of 5.6 mm Tris HCl, 4.4 mm Tris base, 0.05% sodium azide 0.1 mm EDTA, 5 mg/liter
More informationGenerating kisspeptin cell lines to investigate their role in reproduction
Generating kisspeptin cell lines to investigate their role in reproduction Dakota C. Jacobs 1 Jadwiga M. Giebultowicz 2, and Patrick E. Chappell 3 1 Bioresource Research, 2 Department of Integrative Biology,
More informationHIV-1 Dual Infection and Neurocognitive Impairment
HIV-1 Dual Infection and Neurocognitive Impairment Gabriel Wagner, MD Assistant Professor of Medicine Infectious Diseases & Global Public Health UC San Diego HIV-Associated End Organ Damage Antiretroviral
More informationAP Biology. Viral diseases Polio. Chapter 18. Smallpox. Influenza: 1918 epidemic. Emerging viruses. A sense of size
Hepatitis Viral diseases Polio Chapter 18. Measles Viral Genetics Influenza: 1918 epidemic 30-40 million deaths world-wide Chicken pox Smallpox Eradicated in 1976 vaccinations ceased in 1980 at risk population?
More informationChapter 18. Viral Genetics. AP Biology
Chapter 18. Viral Genetics 2003-2004 1 A sense of size Comparing eukaryote bacterium virus 2 What is a virus? Is it alive? DNA or RNA enclosed in a protein coat Viruses are not cells Extremely tiny electron
More informationKEY CONCEPT Germs cause many diseases in humans.
31.1 40.1 Pathogens Infectious Diseases and Human Illness KEY CONCEPT Germs cause many diseases in humans. 31.1 40.1 Pathogens Infectious Diseases and Human Illness Germ theory states that microorganisms
More informationStudy Guide 23, 24 & 47
Study Guide 23, 24 & 47 STUDY GUIDE SECTION 23-3 Bacteria and Humans Name Period Date 1. One bacterial disease that is transmitted by contaminated drinking water is a. Lyme disease b. gonorrhea c. tuberculosis
More informationBiol115 The Thread of Life"
Biol115 The Thread of Life" Lecture 9" Gene expression and the Central Dogma"... once (sequential) information has passed into protein it cannot get out again. " ~Francis Crick, 1958! Principles of Biology
More informationPersistent Infections
Persistent Infections Lecture 17 Biology 3310/4310 Virology Spring 2017 Paralyze resistance with persistence WOODY HAYES Acute vs persistent infections Acute infection - rapid and self-limiting Persistent
More informationHerpesviruses. Virion. Genome. Genes and proteins. Viruses and hosts. Diseases. Distinctive characteristics
Herpesviruses Virion Genome Genes and proteins Viruses and hosts Diseases Distinctive characteristics Virion Enveloped icosahedral capsid (T=16), diameter 125 nm Diameter of enveloped virion 200 nm Capsid
More informationIdentification and Characterization of CD4 T cells actively transcribing HIV RNA in Peripheral Blood
Dale and Betty Bumpers Vaccine Research Center National Institute of Allergy and Infectious Diseases National Institutes of Health Identification and Characterization of CD4 T cells actively transcribing
More informationLentiviral vectors: basic to translational
Biochem. J. (2012) 443, 603 618 (Printed in Great Britain) doi:10.1042/bj20120146 603 REVIEW ARTICLE Lentiviral vectors: basic to translational Toshie SAKUMA, Michael A. BARRY and Yasuhiro IKEDA 1 Department
More informationSleeping Beauty: Current applications and future strategies. CAR-TCR Summit 2017 Partow Kebriaei, MD
Sleeping Beauty: Current applications and future strategies CAR-TCR Summit 2017 Partow Kebriaei, MD Outline Chimeric antigen receptor (CAR) technology Viral versus nonviral vectors Results of current clinical
More informationName Section Problem Set 6
Name Section 7.012 Problem Set 6 Question 1 The viral family Orthomyxoviridae contains the influenza A, B and C viruses. These viruses have a (-)ss RNA genome surrounded by a capsid composed of lipids
More informationAMEY 1. p53 Gene Therapy: A Novel Approach in the Treatment of Cancer
AMEY 1 p53 Gene Therapy: A Novel Approach in the Treatment of Cancer An Honors Thesis by: Suzanne C. Amey Advisor: Dr. Robert O Donnell May 2002 AMEY 2 Outline of Contents I. Introduction II. III. IV.
More informationnumbe r Done by Corrected by Doctor
numbe r 5 Done by Mustafa Khader Corrected by Mahdi Sharawi Doctor Ashraf Khasawneh Viral Replication Mechanisms: (Protein Synthesis) 1. Monocistronic Method: All human cells practice the monocistronic
More informationL I F E S C I E N C E S
1a L I F E S C I E N C E S 5 -UUA AUA UUC GAA AGC UGC AUC GAA AAC UGU GAA UCA-3 5 -TTA ATA TTC GAA AGC TGC ATC GAA AAC TGT GAA TCA-3 3 -AAT TAT AAG CTT TCG ACG TAG CTT TTG ACA CTT AGT-5 OCTOBER 31, 2006
More informationNBP Protocol. Orders: Support: Web: NBP
NBP2-29541 NBP2-29541 Protocol Orders: orders@novusbio.com Support: technical@novusbio.com Web: www.novusbio.com Protocols, Publications, Related Products, Reviews and more: www.novusbio.com/nbp2-29541
More informationVIRAL TITER COUNTS. The best methods of measuring infectious lentiviral titer
VIRAL TITER COUNTS The best methods of measuring infectious lentiviral titer FLUORESCENCE CYCLES qpcr of Viral RNA SUMMARY Viral vectors are now routinely used for gene transduction in a wide variety of
More informationlevels of genes were separated by their expression levels; 2,000 high, medium, and low
Figure S1. Histone modification profiles near transcription start sites. The overall histone modification around transcription start sites (TSSs) was calculated. Histone modification levels of genes were
More informationHUMAN IMMUNODEFICIENCY VIRUS (HIV) AND AIDS
HUMAN IMMUNODEFICIENCY VIRUS (HIV) AND AIDS Mohamed Mahdi MD. MPH. Department of Infectology and Pediatric Immunology University of Debrecen (MHSC) 2015 Historical facts about HIV First presentation in
More information