Gene Therapy (Ch. 26) Flashcards
(26 cards)
What are the 3 purposes for gene therapy?
- exchange abnormal gene for a normal one
- repair an abnormal gene
- alter regulation of a gene
What are the 3 essential elements of gene transfer?
vector, gene to be delivered, target cell
What are the 2 modes of gene therapy?
in-vivo = create gene → transgene packing into virus→ injection into person
ex-vivo = remove stem cells from patient→ viral transduction in lab w/ modified gene in stem cells→ inject cells back into person
Why are viruses commonly used as vectors in gene therapy?
can encapsulate and deliver their genes to human cells pathogenically
Manipulate the virus genome»_space; removing disease-causing genes»_space; insert therapeutic genes
What are the 7 pitfalls of gene therapy?
- Transient/low-level expression
- toxicity
- Immune and inflammatory response
- Difficulty reaching target issue
- Need for precise regulation of gene activity
-Viral reactivation in host - chance vector might stimulate immune system in a way that reduces the gene therapy’s effectiveness
What are the 7 vectors used in gene therapy?
- retroviral
- lentiviral
- adenoviral
- adeno-associated virus
- herpes simplex-virus-1
- liposomes
- naked DNA
What are retroviral vectors?
reverse transcriptase = therapeutic RNA –> DNA –> integrates into host chromosome
What are the advantages and disadvantages of retroviral vectors?
A: integrates therapeutic gene into host genome
D:
- risk of insertional mutagenesis
- Activate proto-oncogene
- ineffective in nondividing cells
What are lentiviral vectors?
can enter nondividing cells through pores in the nuclear membrane (ex. HIV)
What are the advantages and disadvantages of lentiviral vectors?
A: Persistent gene transfer in transduced tissues
D: Might induce oncogenesis
What are adenoviral vectors?
dsDNA viruses, can infect BOTH non-dividing and dividing cells; does not integrate into host genome
What are the advantages and disadvantages of adenoviral vectors?
A: Highly effective in transducing various tissues
-Infect dividing and nondividing cells
D: Viral capsid triggers strong immune responses
- short lifespan
What are associated adenoviral vectors?
ssDNA = can insert genome at a specific site on chromosome 19
What are the advantages and disadvantages of associated adenoviral vectors?
A: activate few inflammatory responses; can enter nondividing cells
D: Limited packaging capacity
What are Herpes simplex virus 1 vectors?
dsDNA that infects neuronal cells
What are the advantages and disadvantages of Herpes simplex virus 1 vectors?
A: large packaging capacity with persistent gene transfer
D: residual cytotoxicity with neuron specificity
What are liposomal vectors?
artificial lipid sphere with an aqueous core
What are the advantages and disadvantages of liposomal vectors?
A: can cross cell membranes
- Transfers many cell types
- large holding capacity
- not stimulate immune response bc no peptides
D: costly$$$
What are naked DNA vectors?
DNA with no proteins, molecules or lipids
What are the advantages and disadvantages of naked DNA vectors?
A: Efficient in gene transfer - limited immunogenicity
D: Transient and low-level expression
What are ribozymes?
RNA molecules with enzyme activity that can cleave mRNA
Which vector is most-commonly used? Why?
associated adenoviral vectors
- can insert genetic material into host genome
- only mild inflammatory response
- can enter non-dividing cells
What are 6 different types of gene therapy?
- Plasmid DNA
- Viral vectors
- Bacterial vectors
- Human gene editing technology (CRISPR)
- Patient-derived cellular gene therapy products
- Liposome
What is CAR-T?
successful cancer therapy
T cells will identify cancer cells = genetically modified to fight off cancer cells
