Gene therapy - MB140P93
Title: Genová terapie
Czech title: Genová terapie
Guaranteed by: Department of Genetics and Microbiology (31-140)
Faculty: Faculty of Science
Actual: from 2021
Semester: winter
E-Credits: 3
Examination process: winter s.:combined
Hours per week, examination: winter s.:2/0, Ex [HT]
Capacity: unlimited
Min. number of students: 5
4EU+: no
Virtual mobility / capacity: no
State of the course: taught
Language: Czech
Level: specialized
Note: enabled for web enrollment
Guarantor: RNDr. Michal Šmahel, Ph.D.
Teacher(s): RNDr. Michal Šmahel, Ph.D.
Opinion survey results   WS schedule   
Annotation -
Gene therapy is a discipline striving for the application of up-to-date knowledge and methods into a clinical practice. It comprises methodological approaches of molecular biology and genetic engineering and also understandings from genetics, immunology, biochemistry, virology, oncology, and other biological and medical fields. In a general part of the course, principles, mechanisms, and potential usage of gene therapy will be explained as well as gene transfer and ethical problems associated with gene therapy. Another part of the course will be focused on the utilization of gene therapy in oncology and the description of main anti-tumor therapeutic procedures. Finally, students will prepare short presentations (about 10 min) about the development of gene therapy for selected non-malignant diseases.
Last update: Šmahel Michal, RNDr., Ph.D. (01.11.2021)
Literature -

Mauro Giacca: Gene Therapy, Springer-Verlag Mailand, 2010

  eBook ISBN    978-88-470-1643-9,  Hardcover ISBN    978-88-470-1642-2,  Softcover ISBN    978-88-470-5555-1,  DOI    10.1007/978-88-470-1643-9

 

Wolfgang Walther (ed.): Current Strategies in Cancer Gene Therapy, Springer International Publishing, 2016

  Hardcover ISBN     978-3-319-42932-8,    eBook ISBN     978-3-319-42934-2,    DOI 10.1007/978-3-319-42934-2

Last update: Schierová Michaela, RNDr., Ph.D. (24.10.2019)
Requirements to the exam -

Outline of student presentations

1. Disease characterization and frequency.

2. Standard therapy and its efficacy.

3. Therapeutic gene/genetic material (including regulatory sequences)

4. Delivery methods

5. Preclinical examination (model)

6. Clinical trials

 

This presentation is a prerequisite for examination.

 

Examination

A written test composed of 50 questions (20 multiple choice questions, 20 questions requiring short answers).

Last update: Šmahel Michal, RNDr., Ph.D. (26.07.2023)
Syllabus -

I. General part
Principles, mechanisms and possibilities of gene therapy; ethical problems
Types of therapeutic nucleic acids (NA)
   - genes encoding proteins 
   - non-coding NA (oligonucleotides, catalytic NA, regulatory NA, aptamers)
Delivery of genetic material
   - viral (retroviruses, adenoviruses, herpetic viruses, adeno-associated viruses)
   - non-viral - physical (electroporation, sonoporation, biolistic delivery)
                   - chemical (liposomes, polymers)
Gene editing

II. Gene therapy of tumors
Regulation of gene expression
Immunotherapy
   - modified T lymphocytes (TCR, CAR)
   - vaccines - DNA and RNA vaccines, recombinant viruses, cell vaccines
Suicide genes
Oncolytic viruses

III. Gene therapy of non-malignant diseases – student presentations
Hematopoietic stem cells
Neurodegenerative diseases
Muscle dystrophy
Cardiac diseases
Viral infections
Ocular diseases
Liver diseases
Lung diseases

 

Last update: Šmahel Michal, RNDr., Ph.D. (24.10.2019)
Learning outcomes -

After successfully completing the course, students will:

·       Define the concept of gene therapy, describe its principles, mechanisms of action, and main applications in clinical practice; list the basic ethical issues associated with gene therapy and the possibilities for misuse.

·       List the main types of therapeutic nucleic acids and describe their structure, mechanism of action, and typical areas of application.

·       Categorize viral and non-viral methods of introducing genetic material into cells; compare the main groups of viral vectors with regard to cell tropism, insertion capacity, integration behavior, and safety; distinguish between physical and chemical methods of non-viral introduction and explain the main mechanisms used.

·       Explain the principle of pseudotyping viral vectors, self-complementary AAV, and basic strategies for constructing viral vectors and preparing production cell lines for their amplification.

·       Explain the main approaches to gene editing; distinguish between NHEJ and HDR as the main mechanisms of DNA break repair and interpret their implications for gene editing; describe the components and mechanism of action of the CRISPR/Cas9 system and Cas9 mutation variants; explain the concept and possibilities of base editing.

·       Explain the principle of gene expression regulation using RNA interference, miRNA, and lncRNA, and list the possibilities for their use in gene therapy.

·       Evaluate the main risks and safety aspects of gene therapy and justify the need to regulate the expression of introduced genes; propose strategies to minimize these risks.

·       Give examples of genes that can be specifically modified in cancer; classify individual approaches to cancer immunotherapy that can be classified as gene therapy.

·       Categorize suicide genes and give examples and mechanisms of their effects; explain the mechanism of the bystander effect and compare different combinations of suicide enzyme/substrate in terms of the bystander effect and effect on non-dividing cells.

·       Describe the basic types of oncolytic viruses and their structural modifications leading to selective replication in tumor cells; list the mechanisms of their antitumor effect and suggest ways to increase their selectivity and efficacy.

·       Define the basic types of antitumor vaccines that fall under gene therapy, describe their construction, mechanism of immune response induction, and possible forms of application; compare the advantages and disadvantages of DNA and RNA vaccines, and suggest ways to increase the effectiveness of DNA vaccination.

·       Describe the structure and function of chimeric antigen receptors (CARs) and synthetic Notch receptors; explain the mechanisms of the antitumor effect of CAR-T/TCR-T cells and analyze the main risks and complications of these therapies, including ways to reduce toxicity and prevent pairing of endogenous and foreign TCR chains.

Last update: Šmahel Michal, RNDr., Ph.D. (19.12.2025)