gene therapy

genetics lecture

gene therapy

a technique that modifies genes to treat or prevent disease

goals of gene therapy

correct defective genes responsible for disease development

early concepts of gene therapy (1960-1980s)

discovery of DNA structure

recombinant DNA technology

discovery of DNA structure

watson and crick’s model paved the way for genetic understanding

recombinant dna technology

1970s: enabled manipulation of DNA

crucial for later gene therapy

first gene therapy trial (1990)

ADA-SCID treatment

• first successful trial for adenosine deaminase deficiency

gene therapy (1990s-2010s)

1999- Jesse Gelsinger

• clinical trial at UPenn with viral gene vectors

  • too much viral gene vector caused him to go into sepsis and die

2000s

• approval of the first gene therapy product in Europe

  • gendicine for head and neck cancers

Recent developments

2017: FDA approval of CAR-T cell therapy for certain leukemias

2020: FDA approval of Zolgensma for spinal muscular atrophy

types of gene therapy

gene addition

gene editing

gene knockdown

gene addition

adding a healthy copy of a gene

gene editing

techniques like CRISPR to modify existing gene

gene knockdown

reducing the expression of a problematic gene

CRISPR

genetic engineering technique used to modify DNA of living organisms

based on bacterial immune system

delivery methods

vectors

types of vectors

viral and non-viral vectors

viral vectors

modified viruses to deliver genes

use a virus that’s been modified so it can’t replicate

examples of viral vectors

adenoviruses

lentiviruses

non-viral methods

liposomes

electroporation

microinjection

how do you choose the right method?

based on target cells, gene size, and treatment goal

applications of gene therapy

genetics disorders

oncological applications

infectious disease

neurological disorders

cardiovascular diseases

eye disorders

genetic disorders

cystic fibrosis

hemophilia

oncological applications

CAR-T cell therapy

oncolytic virus therapy

infectious disease

HIV/AIDS

Hepatitis B

neurological disorders

spinal muscular atrophy (SMA)

parkinson’s disease

cardiovascular diseases

heart disease

eye disorders

retinal dystrophies

cystic fibrosis

targeting the CFTR gene to correct defective chloride transport

experimental therapies are in development using inhaled gene delivery

hemophilia

gene therapy to introduce a functional copy of the F8 or F9 gene

ongoing trials show promise in reducing bleeding episodes

CAR-T cell therapy

engineering t cells to target and destroy cancer cells, in leukemias and lymphomas

oncolytic virus therapy

using modified viruses that selectively infect and kill cancer cells, while sparing normal tissues

HIV/AIDS

gene editing techniques to disrupt CCR5 gene

hepatitis B

investigating gene therapy to eliminate viral reservoirs in the liver

SMA

zolgensma delivers a copy of the SMN1 gene, significantly improving motor function in affected infants

parkinson’s disease

experimental gene therapies aimed at delivering genes that produce neuroprotective factors to prevent neuronal degeneration

heart disease

introducing genes that encode proteins to improve blood flow or promote heart repair post-myocardial infarction

early trials showing promise in improving heart function and reducing scar tissue

retinal dystrophies

luxturna delivers a copy of the RPE65 gene directly to retinal cells, improving vision in pts with specific genetic mutations

challenges and considerations

safety concerns

ethical issues

cost and accessibility

FDA oversight

safety concerns

risk of immune response, insertional mutagenesis

ethical issues

germline v somatic editing

cost and accessibility

high cost of therapies and insurance coverage issues

FDA oversight

approval process for gene therapies

germline editing

modifications made to the genes in germ cells (sperm and eggs) or early embryos

characteristics of germline editing

changes are heritable and passed on to future generations

permanent alterations to genetic makeup of an individual and their offspring

techniques of germline editing

often involves CRISPR-Cas9 or other gene-editing technologies

applications of germline editing

potential to eliminate genetic disorders before birth

ethical considerations are significant due to the implications for future generations

somatic editing

modifications made to non-reproductive cells in an individual

characteristics of somatic editing

changes are not inherited; they affect only the individual treated

often targets specific tissues or organs for therapeutic benefit

techniques of somatic editing

uses CRIPSR-Cas9, viral vectors, other delivery methods

applications of somatic editing

used to treat existing genetic disorders

often seen as more ethically acceptable since effects are not passed to offspring

role of the PA

pt education

interdisciplinary collaboration

pt education

discussing options and implications with pts

interdisciplinary collaboration

working with geneticists and other specialists