Post on 22-Apr-2018
petercelec@gmail.com
2016 Institute of Molecular Biomedicine
www.imbm.sk
Peter Celec
Gene Therapy
Definition
Principles
Classification
Vectors
Clinics
Issues
Gene therapy
Definition
All approaches for the treatment of diseases that use
nucleic acids and genetic engineering
Principles of gene therapy
Gene substitution
Killing of target cells
Mutation repair
Targeted inhibition of gene expression
Principles of gene therapy
Gene substitution
Normal phenotypeDiseased cells
Principles of gene therapy
Killing of target cells
Target cells
Principles of gene therapy
Killing of target cells
Prodrug
Target cells
Principles of gene therapy
Killing of target cells by activation of the immune system
Foreign antigen
Cytokine gene
Target cells
Target cells
Immune cells
Principles of gene therapy
Mutation repair
Diseased cells Normal phenotype
Principles of gene therapy
Targeted inhibition of gene expression
Diseased cellsInhibition
Nobel Prize in Physiology or Medicine 2006
Andrew Z. Fire Craig C. Mello
1/2 of the prize 1/2 of the prize
USA USA
Stanford University School of
Medicine
Stanford, CA, USA
University of Massachusetts
Medical School
Worcester, MA, USA
b. 1959 b. 1960
"for their discovery of RNA
interference - gene
silencing by double-
stranded RNA"
Principles of gene therapy
RNA interference
Classification of gene therapy
According to the used nucleic acid
– DNA based
– RNA based
Classification of gene therapy
According to the target cell type
– Somatic
– Germline
Classification of gene therapy
Classification of gene therapy
According to the approach
– In vivo
– Ex vivo
Classification of gene therapy
According to the approach
Vectors
Viral
Non-viral
Bacterial
Vectors
Viral vectors
Retrovirus
Adenovirus
Adeno-associated virus
Herpesvirus
Alfavirus
...
Non-viral vectors
Naked or coated DNA
Various physico-chemical
transport systems
Non-viral vectors
Plasmids PCR products
Injection of naked DNA
Elektroporation
Gene gun
Lipoplexes
Polyplexes
Oligodeoxynucleotides
Bacterial vectors
Bactofection
– Listeria
– Escherichia
– Salmonella
Alternative gene therapy
Bactofection
Alternative gene therapy
Transkingdom RNAi
Transkingdom RNAi
lysteriolysin
Bacterial vectors and cancer
Targeting organelles
Clinics
1989/1990 – first clinical study
Severe combined immunodeficiency (SCID)
Retroviral vector
Integrating into the chromosome
Ex vivo
Clinics
Clinics
Clinics
Antioxidative gene therapy
Antioxidative gene therapy
DNA vaccination
DNA vaccination - bacteria
Bactofection
Bactofection
Alternative gene therapy
Alternative gene therapy
CRISPR/Cas9
CRISPR/Cas9
CRISPR/Cas9
http://zlab.mit.edu/
Gene therapy issues
Ethics
Gene transfer
– Safety
– Efficiency
– Specificity
– Regulation of expression
Topics
Sleeping Beauty transposon system
AAV induced immune response
Zinc finger endonucleases
SCID GT trial
Ethics – doping, embryonal GT
miRNA for targeting
iPS cells
GT restores vision
GT restores hearing
€ 1.1 million
Our reviews
petercelec@gmail.com