Beneficial Uses of Viruses Part 1: Gene Therapy

What are three beneficial uses of viruses?

gene therapy

cancer prevention

biological control of harmful organisms

What is gene therapy?

inserting, removing, or altering a gene to treat a disease

What are three ways that gene therapy can work?

1. by replacing a mutated gene that causes disease with the wild-type copy of the gene

2. knocking out a mutated gene that is functioning incorrectly

3. introduce a new gene to fight a disease

What kinds of diseases can gene therapy treat? (4)

inheritable

cancers

infectious diseases

any disease that can be corrected with one gene alteration

What must be used to help the DNA enter the cell?

DNA must be packaged within a vector

What is important to consider when choosing a viral vector?

cell tropism

genome size

intergration

immunogenicity

pathogenicity

Why is cell tropism important when choosing a viral vector?

gene therapy needs to get into the right cell type

Why is genome size important when choosing a viral vector?

the virus must have the coping capcity to insert the gene of interest

What viruses are approved as viral vectors of gene therapies?

adenovirus, aav, retrovirus, lentivirus, hsv

Why are lentiviruses good vectors?

intergrates into host genome DNA

slow replicating eveloped retrovirus

What is the process of lentiviral vectors?

production plasmids, transfection, lentiviral vectors, transduction, in vivo or in vitro delivery

What are three different types of gene therapy delivery?

ex vivo somatic

in vivo somatic

germline

How does ex vivo gene therapy work?

cells taken from the patient, viral-vector transformation, expansion in culture, infusion

How does in vivo gene therapy work?

viral vector is injected directly

How does germline gene therapy work?

introducing gene into germline cells allows therapy to be heritable and passed down (not currently used for humans)

What is an example of ex vivo gene therapy?

hematopoietic stem cells removed from SCID patients, treated and put back into the patient

What is an example of in vivo gene therapy?

cystic fibrosis patients lungs are treated in vivo

What are the two approaches of gene therapy locations?

1. insertion into a random location within the host genome

2. gene targetting

What are some non-viral gene therapy vectors? (6)

naked DNA, electroporation, gene gun, sonoporation, lipoplexes, nanoparticles

What's the problem with non-viral gene therapy vectors?

specificity - best in ex vivo

efficiency - low levels of transfection

What are the most common viral vectors in clinical trials?

adenovirus, adeno-associated virus, lentivirus

What is Glybera?

used to treat lipoprotein lipase deficiency

What type of viral vector does Glybera use?

adeno-associated virus

What are some pros of using adeno-associated virus?

low immunogenicity

no pathogenicity

integration of a gene into a specific site of the host genome

What is Luxturna?

an approved adeno-associated virus vector gene therapy

What does Luxterna treat?

biallelic RPE65 mutation-associated retinal dystrophy

What is Zolgensma?

an adeno-associated viral vector gene therapy spinal muscular atrophy

What are some complications with gene therapy? (2)

1. differentiated cells have variant gene expression

2. some cells have higher turnover rates