Pharma Exam 4: Gene Therapy (11)

Gene Therapy

Using genes as medicine to reprogram cells to prevent or cure disease

Delivery Systems

1. Retrovirus

2. Adenovirus

3. Other Virus (Herpes, HIV)

4. Plasmid

5. Microspheres

6. Liposomes

CRISPR/Cas9

Based on system used by bacteria to protect themselves from infection by viruses

Cas9 is nuclease enzyme that uses a guide RNA to cut DNA

Change the guide RNA to cut any point in the DNA

Unzips the DNA and matches to RNA, cell tries to repair the cut

This repair can lead to mutations that disable the gene to silence it.

If you add in another piece of DNA with the desired sequence, making a new, usable version/fixing the gene.

Factors in Selection of Delivery System (5)

Capacity - size of gene

Efficiency - transfection-rate and integration-rate

Safety - Effect on endogenous genes, spread of virus

Selectivity - No expression of other (viral) genes

Lifetime - practicability

Gene Therapy v.s. Cell Therapy

Cell Therapy (Ex vivo) - Remove cells from patient, inject gene-carrying vector in cells, generation of GMCells in vitro, treat patient with genetically modified cells

Gene Therapy (In vivo) - Treat patient with gene-carrying vector (GCV), transfection of GCV into cells, generation of genetically modified cells in vivo

For a generic to make it to the market…

it has to show exactly the same PK profile