Gene and Cell Therapy
Code: 101969 ECTS Credits: 6| Degree | Type | Year |
|---|---|---|
| 2500890 Genetics | OT | 4 |
Contact
- Name:
- Maria Fatima Bosch Tubert
- Email:
- fatima.bosch@uab.cat
Teachers
- Verónica Jimenez Cenzano
Teaching groups languages
You can view this information at the end of this document.
Prerequisites
There are no prerequisites to attend this course. However, to facilitate the student’s understanding of the subject matter and the achievement of the learning goals proposed, it is advisable that the student has previous knowledge on Cellular Biology, Genetics, Molecular Biology and Recombinant DNA technology.
It is also advisable that the students have basic knowledge of English, so that they can use the information sources of the field, which are mostly in this language.
Objectives and Contextualisation
The objective of the subject “Gene and Cell Therapy” is to provide the students with up-to-date knowledge in the methodologies available for the genetic engineering of cells for therapeutic purposes. Thus, the content of the subject will cover the following topics: Description of in vivo and ex vivo gene therapy; Study of the different vectors used for viral and non-viral gene transfer and their respective advantages and shortcomings; study of the possible routes of administration of the vectors and the applications to the treatment of hereditary and non-hereditary human diseases. Description of cell therapy. Transplant of fully differentiated somatic cells (pancreatic islets, hepatocytes, and bone marrow). Transplant of pluripotent stem cells (embryonic and adult). Sources of cells for cell therapies. Therapreutic applications of cell therapies. Biosafety, ethics and legal aspects associated to the use of cell therapies in humans.
Competences
- Act with ethical responsibility and respect for fundamental rights and duties, diversity and democratic values.
- Assume ethical commitment
- Be able to analyse and synthesise.
- Be able to communicate effectively, orally and in writing.
- Be sensitive to environmental, health and social matters.
- Define mutation and its types, and determine the levels of genic, chromosomal and genomic damage in the hereditary material of any species, both spontaneous and induced, and evaluate the consequences.
- Describe and interpret the principles of the transmission of genetic information across generations.
- Describe the organisation, evolution, inter-individual variation and expression of the human genome.
- Make changes to methods and processes in the area of knowledge in order to provide innovative responses to society's needs and demands.
- Perceive the strategic, industrial and economic importance of genetics and genomics to life sciences, health and society.
- Show an understanding of the genetic bases of cancer.
- Take account of social, economic and environmental impacts when operating within one's own area of knowledge.
- Take sex- or gender-based inequalities into consideration when operating within one's own area of knowledge.
- Take the initiative and demonstrate an entrepreneurial spirit.
Learning Outcomes
- Act with ethical responsibility and respect for fundamental rights and duties, diversity and democratic values.
- Assume ethical commitment
- Be able to analyse and synthesise.
- Be able to communicate effectively, orally and in writing.
- Be sensitive to environmental, health and social matters.
- Describe the structure and variation of the human genome from a functional, clinical and evolutionary perspective.
- Determine the genetic basis and calculate the risk of recurrence of human illnesses.
- Make changes to methods and processes in the area of knowledge in order to provide innovative responses to society's needs and demands.
- Recognise genic, chromosomal and genomic anomalies in humans and evaluate the clinical consequences.
- Recognise the strategic importance of genetic progress in the field of human health, especially applications of the genomic to personalised medicine, pharmacogenomics and nutrigenomics.
- Show an understanding of the genetic bases of cancer.
- Take account of social, economic and environmental impacts when operating within one's own area of knowledge.
- Take sex- or gender-based inequalities into consideration when operating within one's own area of knowledge.
- Take the initiative and demonstrate an entrepreneurial spirit.
Content
Knowledge on the following topics will be imparted during the theoretical classes:
TOPIC 1
Molecular basis of Gene Therapy. Gene therapy in vivo and ex vivo. Introduction to Cell therapy.
TOPIC 2
Retroviral vectors derived from murine leukaemia virus. Retroviral replicative cycle. Production of retroviral vectors. Retrovirus-mediated gene expression. Applications.
TOPIC 3
Lentiviral vectors (LV). Genomic organization of lentiviruses. Production of lentiviral vectors. Properties. Applications.
TOPIC 4
Adenoviral vectors (Ad). Structure and genomic organization of adenoviruses. Production of adenoviral vectors. Properties. Applications. Production of less immunogenic later generation adenoviral (HD-Ad). Oncolytic adenoviral vectors.
TOPIC 5
Adeno-associated viral vectors (AAV). Biology of adeno-associated viruses. Production of adeno-associated virus-derived recombinant vectors. Properties. Applications.
TOPIC 6
Non-viral vectors (I). Use of cationic liposomes in gene therapy. Gene transfer with cationic polymers. Receptor-mediated gene transfer.
TOPIC 7
Non-viralvectors (II). Transfer of plasmidic DNA in solution to the muscle. Electrotransfer. Transfer of plasmidic DNA in solution to the liver through hydrodynamic procedures. Applications.
TOPIC 8
Interference RNA (siRNA). Gene therapy based on the use of siRNA. Applications.
TOPIC 9
Genome editing. Different types of nucleases: Meganucleases, Zinc-finger nucleases, TALENs, CRISPR Technologies. Applications in the field of Gene Therapy.
TOPIC 10
Ex vivo gene therapy; hematopoietic stem cells.
TOPIC 11
Introduction to Embryonic Stem Cells (ES cells). Differentiation of cells. Clinical Applications of ES cells.
TOPIC 12
Adult stem cells and their applications.
TOPIC 13
Reprogramming and Induced Pluripotent Stem Cells (iPS).
TOPIC 14
Gene therapy for hereditary monogenic diseases: Immunedeficiencies. Lysosomal diseases. Cystic fibrosis. Eye diseases. Haemophilia. Muscular dystrophies. Other diseases.
TOPIC 15
Gene therapy for cancer. Immunotherapies. Use of suicide genes. Antiangiogenic gene therapies. Use of tumour suppressor genes. Use of antisense sequences. Other therapeutic strategies.
TOPIC 16
Gene therapy for diabetes mellitus. Gene therapy for cardiovascular diseases. Gene therapy for neurodegenerative diseases.Gene therapy for infectious diseases (AIDS, hepatitis). DNA vaccines.
TOPIC 17
Cell therapies for the regeneration of bone and cartilage.
TOPIC 18
Cell therapies for the regeneration of skin. Cell therapies for the regeneration of eye diseases.
TOPIC 19
Cell therapies for Parkinson disease and other Central Nervous System diseases.
TOPIC 20
Cell therapies for diabetes mellitus and cardiovascular diseases.
TOPIC 21
Cell and Gene Therapy Clinial protocols. Phases of a clinical trial. European regulatory bodies, American regulatory bodies. Ethical aspects of gene and cell therapies.
Three exercises are proposed for the laboratory practice classes. The first assignment is the design of a gene or cell therapy strategy for a given disease, from design of the gene or cell product to proof-of-concept studies and translational studies that allow a clinical trial in humans.This exercise is proposed as a review of all the concepts introduced in the theory classes. The second proposed activity allows students to acquire experience in the use of laboratory animals in gene and cell therapy studies. Finally, in the third proposed activity we show students how to perform a partial hepatectomy for gene therapy approaches directed to the liver.
Content of the laboratory practice classes:
- Design of a gene or cell therapy strategy; discussion of thedifferent options.
- Introduction to the use of laboratory animals in gene and cell therapy studies.
- Methods and routes of administration of viral and non-viral vectors.
*Unless the requirements enforced by the health authorities demand a prioritization or reduction of these contents.
Activities and Methodology
| Title | Hours | ECTS | Learning Outcomes |
|---|---|---|---|
| Type: Directed | |||
| Oral presentations | 9 | 0.36 | 2, 3, 4, 5, 14 |
| Practical lessons | 12 | 0.48 | 2, 3, 4, 5, 14 |
| Theorical lessons | 34 | 1.36 | 2, 3, 4, 5, 14 |
| Type: Supervised | |||
| Tutorials | 5 | 0.2 | 2, 3, 4, 5, 14 |
| Type: Autonomous | |||
| Individual study time | 74 | 2.96 | 2, 3, 4, 5, 14 |
| Oral presentations | 10 | 0.4 | 2, 3, 4, 5, 14 |
The subject “Gene and Cell Therapy” consists of theory and laboratory classes, and tutored oral presentations of relevant literature. The formative activities of the subject are complementary.
Theoretical classes
The contents of the theoretical classes will be imparted by a Professor in a series of master classes supported by audio-visual material. The slides used by each professor in each class will be available to the students through the subject’sCampus Virtual/Moodle. These master classes will constitute the main form of transfer of theoretical contents. Students are advised to periodically consult the books and links suggested in the Bibliography section of this document and at the Campus Virtual/Moodle to consolidate and clarify, if necessary, the contents explained in class.
Laboratory practice classes
The laboratory practice classes have been designed to help students get familiarized with the methodologies used in the field of gene therapy and have a direct experience in the handling of laboratory animals for gene therapy studies. We expect that, during these laboratory practice classes, students will be able to experience a “real world” experimental situation. We would like students to experience the excitement associated to research in the field of gene therapy.
The laboratory practice classes are composed of 3 sessions of 4 h each (from 3PM to 7PM), during which students will work in groups of 2 people under the supervision of an experienced professor. The dates assigned to each laboratory practice group will be published in the subject’s Campus Virtual/Moodle with sufficient anticipation.
Attendance to laboratory practice classes is mandatory.
The laboratory practice guide will be available through the Campus Virtual/Moodle. Students must bring their own lab coat, a waterproof marker and the Laboratory Practice Guide to each laboratory practice class.
Oral presentations of selected papers
Students will analyse and discuss in an oral presentation in front of the whole class a selected recent scientific publication on gene or cell therapy published in a recognized international scientific journal. To this end, students will pair with a fellow classmate. During the process of analysis of the paper’s content and preparation of the oral presentation, students will be tutored by researchers with experience in the field of gene and cell therapy. Students will have 10 minutes for the oral presentation, equally divided amongst the members of the group, plus 5 minutes for questions (total of 15 minutes). The objective of this evaluating activity is that students get used -under the supervision of a tutor- to the process of searching, reading and understanding of scientific literature, and if necessary, develop a critical view on the figures, tables and results described in the publication. On the other hand, with this activity students will increase their knowledge of the current applications of gene and cell therapy technologies.
Tutoring
The oral presentations of selected papers will be tutored. In addition, upon request from the students, individualized tutoring will be available throughout the course. The objective of this sessions will be to help the student resolve doubts and review basic concepts and to provide them with advice on sources of information and the best way to discuss scientific results in public.
UAB Surveys
15 minutes of one class will be allocated for the response of the UAB institutional survey.
Annotation: Within the schedule set by the centre or degree programme, 15 minutes of one class will be reserved for students to evaluate their lecturers and their courses or modules through questionnaires.
Assessment
Continous Assessment Activities
| Title | Weighting | Hours | ECTS | Learning Outcomes |
|---|---|---|---|---|
| Attendance to the oral presentations of research papers | 10% | 0 | 0 | 2, 3, 4, 5, 14 |
| Examination of Laboratory classes | 15% | 1 | 0.04 | 2, 3, 4, 5, 14 |
| Final examination of theoretical classes | 50% | 3 | 0.12 | 2, 3, 4, 5, 6, 7, 9, 10, 11, 14 |
| Oral presentations of selected research papers | 15% | 1 | 0.04 | 1, 2, 3, 4, 5, 8, 12, 13, 14 |
| Self-study exercise | 10% | 1 | 0.04 | 2, 3, 4, 5, 14 |
To pass the course, students must achieve a final score of 5 points (over a total of 10 points) and must attend the laboratory practice classes. The evaluation activities are:
1.- Final examination of theoretical classes
Accounts for 50% of the final score (5 points out of 10). Assessment will consist of a written examination, under the format of a True or False test, on topics explained during the theoretical classes. A score greater than 2.5 in this examination is required to pass the course.
There will be a Second Chance/Recovery Exam, under the same format as the original exam.
2.- Examination of Laboratory classes
Accounts for 15% of the final score (1.5 points out of 10). Assessment will consist of a written examination, under the format of a True or False test, on topics explained during the practical classes. It will be held the same day of the theoretical classes examination.
Attendance to practical sessions (or field trips) is mandatory. Students missing more than 20% of programmed sessions will be graded as "No Avaluable.
3.- Self-study exercise
Accounts for 10% of the final score (1 point out of 10). Assessment will consist of an exercise that the student will have to develop on their own. Details will be posted online in the "Campus Virtual" at the end of April.
4.- Oral presentations of selected research papers
Accounts for 15% of the final score (1.5 points out of 10). Students will be evaluated individually, both on their performance during the oral presentation of the selected paper and on the audio-visual material that they prepared to support theirgroup presentation.
5.- Attendance to the oral presentations of research papers
Accounts up to 10% of the final score (1 point out of 10). Both attendance and participation in the scientific discussions of the sessions will be evaluated, following the scale:
Attendance 90-100% = 1 point
Attendance 80-89% = 0,8 points
Attendance 70-79% = 0,7 points
Attendance 60-69% = 0,6 points
Attendance 50-59% = 0,5 points
Attendance 0-49% = 0 points
6.-The review of the theory and practical exams qualifications will be carried out in person on a day and time communicated via the virtual campus, some days after the publication of the grades.
Single evaluation: The theory and practical exam will take place on the same day. Attendance to practical classes is mandatory. For the oral presentation of research papers, in the event that the ENTIRE GROUP that makes the presentation is eligible for the single evaluation, the group may make the oral presentation on the same day of the theoretical and practical exam, once the exam is finished. Students who take single assessment and who cannot attend the oral presentations, can optionally obtain the point of attendance to the oral presentations of selected research papers by performing an analysis of an article or an activity related to the topic of the subject, the same day of the exam once the exam is finished.
Bibliography
1- Gene and Cell Therapy. Therapeutic Mechanisms and Strategies. 2nd Edition. Edited by Nancy Smyth Templeton. Marcel Dekker, Inc. 2004.
2- Gene Therapy technologies, aplications and regulations. From Laboratory to Clinic. Edited by Anthony Meager. John Wiley & Sons, LTD. 1999.
3- Gene Therapy Protocols. 2nd Edition. Edited by Jeffrey R. Morgan. Humana Press. 2002.
4- Human Molecular Genetics 2. T. Strachan i A.P. Read. John Wiley & Sons, Inc., Publication. 1999.
5- Cell Therapy. D. Garcia-Olmo, J.M. Garcia-Verdugo, J. Alemany, J.A. Gutierrez-Fuentes. McGraw-Hill Interamericana. 2008.
6- Gene and Cell Therapy. Therapeutic Mechanisms and Strategies. Second edition, Revised and Expanded. N.S. Templeton. Marcel Dekker, Inc. 2004.
Software
Not applicable
Language list
| Name | Group | Language | Semester | Turn |
|---|---|---|---|---|
| (PLAB) Practical laboratories | 441 | Catalan/Spanish | second semester | afternoon |
| (PLAB) Practical laboratories | 442 | Catalan/Spanish | second semester | afternoon |
| (PLAB) Practical laboratories | 443 | Catalan/Spanish | second semester | afternoon |
| (PLAB) Practical laboratories | 444 | Catalan/Spanish | second semester | afternoon |
| (PLAB) Practical laboratories | 445 | Catalan/Spanish | second semester | afternoon |
| (PLAB) Practical laboratories | 446 | Catalan/Spanish | second semester | afternoon |
| (SEM) Seminars | 441 | Catalan/Spanish | second semester | morning-mixed |
| (TE) Theory | 44 | Catalan/Spanish | second semester | morning-mixed |