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Module 1: Gene Delivery e Altre Varianti

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Carriers are needed for putting genes inside cells: Viruses, Polymers or Lipids.

Viral Vectors

Advantages
High transfection efficiency
Natural tropism
Evolved mechanisms for endosomal escape
Natural transportation mechanism of DNA into the nucleus
Disadvantages
The strong immune reaction against viral proteins prohibit multiple administrations
Possibility of chromosomal insertion and proto-oncogene activation
Complicated synthesis process
Limitation on gene size
Toxicity, contamination of the live virus
Non-Viral Vectors
Advantages
Low immunogenicity
Can be made to be non-toxic
Easy to synthesis: quality control for mass production
Potentially targetable
No limit on plasmid size
No integration: can be administered as drugs
Disadvantages
Low transfection efficacy
Currently, most vehicles are toxic at high dosages
No natural tropism, endosomal escape or nuclear transport mechanisms
How are genes used as vaccines?
DNA vaccines: Genes encoded for specific antigenic proteins of interest. Instead of delivering the pathogen or recombinant protein, the host cells themselves produce the antigen

Immunization against allergies:
- Sensitization
- Re-exposure
- IgE mediated anaphylaxis
- Immunize
- IgG2a mediated Th1 response
- Allergen Exposure

Gene Carriers:
- Polyethyleneimine
- Chitosan
- PAMAM-dendrimers
- Novel cationic polymers

Cancer Vaccines:
- Prophylactic vaccine- prevent liver and cervical cancers
- Therapeutic vaccine- increase the immune response against tumour antigens