Important notice
The course guide is provisional.
The PDF version of the course guide may take a few days to become available in the DDD.
Transgenesis and Gene Therapy: from the Animal to the Clinic
Code: 45558Credits: 9
| Degree programme | Type | Course |
|---|---|---|
| Advanced Biotechnology | OP | 1 |
Contact lecturer
- Name :
- Fàtima Bosch Tubert
- Email :
- fatima.bosch@uab.cat
Teaching staff
- Miguel Chillón Rodriguez
- Verónica Jimenez Cenzano
- Víctor Nacher Garcia
- Marc Navarro Beltran
- Jesús Ruberte Paris
- Ana Carretero Romay
- Assumpció Bosch Merino
Group languages
You can consult this information at the end of the document.
Prerequisites
Graduate in the field of life sciences, for example:
Biology, Biochemistry, Biomedicine, Biotechnology, Pharmacy, Genetics, Medicine, Veterinary Medicine.
Objectives
The student will gain insight into:
- Technologies used to generate transgenic animals overexpressing specific transgenes or mutant models with specific endogenous genes modified (knockout and knockin animal models).
- Application of the aforementioned technologies in biomedicine, biotechnology and livestock.
- Current legislation for animal experimentation
- Mouse anatomy and embryology in order to understand the embryonic development of organs and to analyze morphological/anatomical abnormalities in genetically modified mouse models.
- In vivo and ex vivo gene therapy, including characteristics of the different types of vectors (viral and non-viral) used for gene transfer as well as their advantages and disadvantages, administration routes and applications of gene therapy in the treatment of hereditary and non-hereditary human diseases.
Learning outcomes
- CA13 (Apply techniques for modifying living organisms or parts thereof to improve pharmaceutical and biotechnological processes and products, or to develop new products.) Apply techniques for modifying living organisms or parts thereof to improve pharmaceutical and biotechnological processes and products, or to develop new products.
- CA14 (Work as a team to plan projects in the fields of transgenesis and gene therapy associated with current challenges in biochemistry, molecular biology and biomedicine, while demonstrating ethical responsibility and respect for fundamental rights and duties, diversity and democratic values.) Work as a team to plan projects in the fields of transgenesis and gene therapy associated with current challenges in biochemistry, molecular biology and biomedicine, while demonstrating ethical responsibility and respect for fundamental rights and duties, diversity and democratic values.
- KA13 (List the molecular foundations of in vivo and ex vivo gene therapy.) List the molecular foundations of in vivo and ex vivo gene therapy.
- KA14 (Identify the anatomy and embryology of the mouse, as well as morphological alterations in genetically manipulated mice.) Identify the anatomy and embryology of the mouse, as well as morphological alterations in genetically manipulated mice.
- KA15 (Identify the different technologies for obtaining transgenic animals and for vivo and ex vivo gene therapy, as well as the ethical implications of this field.) Identify the different technologies for obtaining transgenic animals and for vivo and ex vivo gene therapy, as well as the ethical implications of this field.
- SA14 (Relate the different methodologies used to obtain transgenic animals that enable the overexpression, blocking or modification of endogenous genes in a ubiquitous or tissue-specific manner.) Relate the different methodologies used to obtain transgenic animals that enable the overexpression, blocking or modification of endogenous genes in a ubiquitous or tissue-specific manner.
- SA15 (Appropriately use the different types of vectors for gene transfer within the context of gene therapy.) Appropriately use the different types of vectors for gene transfer within the context of gene therapy.
- SA16 (Properly analyse the molecular or physiological alterations of a transgenic animal, as well as the results of clinical gene therapy trials in humans.) Properly analyse the molecular or physiological alterations of a transgenic animal, as well as the results of clinical gene therapy trials in humans.
Contents
PART 1. MOUSE MORPHOLOGICAL PHENOTYPING
By J. Ruberte, A. Carretero, M. Navarro and V. Nacher. Dept. Animal Health and Anatomy, UAB
1. Anatomic Terminology and Regions
2. Development and Placenta
3. Osteology
4. Arthrology and Miology
5. Cardiovascular System
6. Repiratory Apparatus
7. Digestive Apparatus
8. Urinary Organs
9. Male and Female Genital Organs
10. Nervous System
11. Visual Organ
12. Vestibulocochlear Organ
PART 2: TRANSGENIC ANIMALS AND GENE THERAPY
By F. Bosch and Verónica Jiménez.
Dept. Biochemistry & Molecular Biology, UAB
Part 2.1. Transgenic Animals:
1. Generation of transgenic animals by pronuclear microinjection.
2. Constitutive and conditional (tissue specific and/or inducible) Knockout/in animals.
3. Generation of Knockout/in animals by Genome Edition with ZFNs, TALENs and CRISPR/Cas9
4. Cloned animals by nuclear transfer. Aplications.
5. Consortia for genome mutagenesis and mouse phenotyping: Mouse Clinics.
6. Management of transgenic animal colonies. Current legislation on animal experimentation.
7. Aplications of transgenic animal technology in the study of diabetes, obesity, inherited diseases…
Part 2.2. Gene Therapy:
1. Introduction to the gene therapy field.
2. Characteristics of adenoviral vectors. Applications.
3. Characteristics of recombinant vectors derived from adenoassociated viruses. Applications in gene therapy for diabetes mellitus.
4. \"Ex vivo\" Gene Therapy: retroviral and lentiviral vectors. Applications.
5. Non-viral gene therapy. Applications.
6. Gene Therapy for Hereditary Diseases. Gene Therapy for Mucopolysaccharidosis (MPS).
7. Invivo” genome editting.
PART 3. INTRODUCTION AND DESIGN OF GENE THERAPY CLINICAL TRIALS FOR THE TREATMENT OF HUMAN DISEASES
By M. Chillon and A. Bosch, Dept. Biochemistry & Molecular Biology, UAB
Invited speaker: Ramon Alemany, Institut Català d’Oncologia (ICO)
1-Introduction to clinical trials. Factors to consider in the design of clinical trials of gene therapy. M Chillon
2-Development and production of vectors for clinical trials. M Chillon
3-Regulation on the use of Genetically Modified Organisms. Biosafety level and quality of production (GMP and GLP conditions). M Chillon
4-Adenoassociats vectors in clinical trials. Increased tissue specificity using pseudotyped AAV vectors and specific promoters. Immune response. A Bosch
5-Vectors derived from herpes simplex virus in clinical trials. A Bosch
6-Advantages and disadvantages of retroviral and lentiviral vectors in clinical trials. ABosch
7-Ongoing clinical trials for specific diseases: Haemophilia, ß-Thalassemia, Primary Immunodeficiencies, Cystic Fibrosis, Duchenne Muscular Dystrophy, lysosomal storage diseases, neurodegenerative diseases, blindness, cancer, etc. A Bosch, M Chillon
Learning activities and methodology
| Title | Hours | ECTS | Learning outcomes |
|---|---|---|---|
| Literature search and study for exams | 120 | 4.8 | CA13, KA13, KA14, SA14, SA16 |
| Preparation of oral presentations and lab practices | 44 | 1.76 | CA14, KA15, SA15, SA16 |
| Lectures and lab practices | 55 | 2.2 | CA13, KA13, KA14, KA15, SA14, SA16 |
Combination of lectures and laboratory practices and presentation of a project supervised by the teacher.
Theory 72%
Laboratory 11%
Supervised work 14%
Tutoring 3%
UAB Surveys
15 minutes of one class will be allocated for the response of the UAB institutional survey.
Assessment
Continuous assessment activities
| Title | Weight | Hours | ECTS | Learning outcomes |
|---|---|---|---|---|
| Attendance and active participation in lectures | 10% | 0 | 0 | CA13, KA13, KA14, KA15, SA15, SA16 |
| Theorical and practical tests (part 1 and 3) | 50% | 4 | 0.16 | CA13, KA13, KA14, SA14, SA15, SA16 |
| Oral defence of selected papers (part 2) | 32% | 2 | 0.08 | CA14, KA13, KA14, SA15, SA16 |
| Attendance to laboratory practices (part 1) | 8% | 0 | 0 | CA14, KA14, SA14, SA15, SA16 |
The evaluation of the module will be based on work done by students, attendance and class participation, practices, oral defence of a scientific paper and the grade of exams at the end of the course.
To be eligible for the retake process, the student should have been previously evaluated in a set of activities equaling at least two thirds of the final score of the course or module. Thus, the student will be graded as \"No Avaluable\" if the weighthin of all conducted evaluation activities is less than 67% of the final score.
In this course, the use of Artificial Intelligence (AI) technologies is not permitted at any stage. Any assignment that includes content generated by AI will be considered a breach of academic integrity and may result in a partial or total penalty to the activity's grade, or more severe disciplinary sanctions in serious cases.
Any irregularity committed during an assessment activity (academic misconduct, plagiarism, or improper use of AI, unless such use is expressly authorized in the course syllabus) that may lead to a significant alteration of the grade will result in that activity being graded as 0. If the course syllabus stipulates that obtaining a minimum mark in this assessment is an essential requirement to pass the course, or if multiple irregularities occur in the assessment activities of the same course, the final grade for the course will be 0. Furthermore, disciplinary proceedings may be initiated against any student who incurs any of these irregularities.
Bibliography
Biblography
Gene and Cell Therapy. Therapeutic and Strategies. 2nd Edition. Edited by Nancy Smith Templeton, 2000.
Molecular Medicine. Edited by R.J. Trent. 3rd Edition. Elsevier Academic Press. 2005.
DNA Pharmaceuticals. Formulation and Delivery in Gene Therapy.
DNA Vaccination and Immunotherapy. Martin Scheef. WiLey-VCH Verlay GmbH &Co.KgaA, 2005.
Gene Therapy Technologies, applications and regulations. From Laboratory to Clinic. Edited by Anthony Meager. John Wiley & Sons, LTD, 1999.
Gene Therapy. Therapeutic Mechanisms and Strategies. Edited by Nancy Smith Templeton, Danilo D Basic. Marcel Dekker, Inc, 2000.
Gene Therapy Protocols. 2nd Edition. Edited by Jeffrey R Morgan Humana Press, 2002.
Human Molecular Genetics 2. T Strachan & AP Read. John Wiley & Sons, Inc., 1999.
Molecular Biotechnology Principles and Applications of Recombinant DNA. Bernard R Glick and Jack J Pasternak. Washington ASM Press, 1994.
The anatomy of the laboratory mouse. M. J. Cook. Academic Press, 1965
A color atlas of sectional anatomy of the mouse. T. Iwaki, H Yamashita, T. Hayakawa. Braintree Scientific, Inc., 2001.
The atlas of mouse development. M. H. Kaufman. Academic Press, 1995.
Transgenic animals. Generation and use. L.M. Houdebine. Harwood Academic Publishers 1997.
Manipulating the mouse embryo. A laboratory manual. 3rd Edition. A Nagy, et al. Cold Spring Harbor Laboratory Press, 2003.
Mouse genetics and transgenics. A practical approach. Ed. IJ Jackson & CM Abbott. Oxford University Press, 2000.
Gene Targeting. A practical approach. 2nd Edition. Ed. AL Joyner. Oxford University Press, 2000.
Transgenesis Techniques. Principles and Protocols. Edited by: Alan R. Clarke. Humana Press. 2002. (2nd Edition).
Gene Knock-out Protocols. Edited by: Martin J. Tymms and Ismail Kola. Humana Press. 2001.
Embryonic Stem Cells. Methods and Protocols. Edited by: Kursad Turksen. Humana Press.2002.
HumanMolecular Genetics2. T. Strachan i A.P. Read. John Wiley & Sons, Inc., Publication. 1999.
Morphological Mouse Phenotyping: Anatomy, Histology and Imaging. J. Ruberte, A. Carretero and M. Navarro. Ed. Medica Panamericana, 2016.
X-Ray Annotation Mouse Atlas. J Ruberte et al.IMPC (Doctor Herriot SL), 2021.
Web links
Gene Therapy Clinical Trials Worldwide www.wiley.co.uk/genmed/clinical
Human Genome Project Information
www.ornl.gov/sci/techresources/human_genome/medicine/genetherapy.shtml
The anatomy of the laboratory mouse jaxmice.jax.org/library/notes/498.html
International Society for Transgenic Technologies
www.transtechsociety.org
Transgenesis en mamíferos
www.cnb.uam.es/~transimp/index2.html
EUMORPHIA
www.eumorphia.org
TBASE (The Transgenic/Targeted Mutation Database)
http://tbase.jax.org/
Database of Gene Knockouts
http://www.bioscience.org/knockout/knockhome.htm
BioMedNet Mouse Knockout Database
http://biomednet.com/db/mkmd
Specialized journals
Nature (www.nature.com)
Nature Medicine (www.nature.com/nm/)
Nature Biotechnology (www.nature.com/nbt/)
Nature Genetics (www.nature.com/ng/)
Proc. Natl. Acad. Sci. USA (www.pnas.org)
Journal Clinical Investigation (www.jci.org)
Cancer Gene Therapy (www.nature.com/cgt)
Current Gene Therapy (bentham.org/cgt)
Gene Therapy (www.nature.com/gt)
Gene Therapy & Molecular Biology www.gtmb.org/index_gtmb.html
Gene Therapy & Regulation www.vsppub.com/journals/jn-GenTheReg.html
Human Gene Therapy (www.liebertonline.com/loi/hum)
The Journal of Gene Medicine
www3.interscience.wiley.com/cgi-bin/jhome/10009391
Journal of Molecular Therapy
link.springer-ny.com/link/service/journals/00109
Journal of Controlled Release
www.sciencedirect.com/science/journal/01683659
Journalof Virology (jvi.asm.org)
Molecular Therapy www.sciencedirect.com/science/journal/15250016
Software
Not applicable
Course groups and languages
The information provided is provisional until November 30. After this date, you will be able to consult the language of each group through this link. To access the information, you will need to enter the course CODE