the great story of gene therapy
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ReferencesGene Therapy Industry Report 2021. Labiotech. June 2021.Jef Akst. Targeting DNA. The Scientist. | Lucy Reading-Ikkanda. Delivering New Genes. June 2012.Ansar Karimian et al. CRISPR/Cas9 technology as a potent molecular tool for gene therapy. Journal of cellular Physiology. January 2019.
Significant Advancements
over the last decadeScene 1
1989First approved protocol to use gene transfer into humans
2003The complete sequence of the human genome is identified
2009Intensive research to increase vector safety
2016First ex-vivo gene therapy approved
2019First gene therapies approved for the treatment of SMA (Zolgensma) and β-thalassemia (Zynteglo)
1972Gene Therapy concept is discovered by Friedmann and Robin
2008First adenovirus gene therapy complete phase III clinical trial
2012First gene therapy approved in Europe
2017First gene therapy approved in the USA
1990First clinical trial to deliver a therapeutic gene is achieved
in the USA
Sensitivity Robustness Sample availability
Selectivity Sample stability
Challenges
Oncology
>1400 >400
Neurological Disorders
>300
Genetic Disorders
>350
Others
Therapeutic areas
ApproachesReplacing
A mutated gene
InactivatingA mutated gene
IntroducingA new gene
> 2400Product
candidates
>1350Preclinical
>300Phase I
>250Phase II
>50Phase III
20 approved
gene therapies
ApproachesReplacing
A mutated gene
InactivatingA mutated gene
IntroducingA new gene
Long TermSafety
EfficacyOver Time
NeutralizingImmune
Responses
ManufacturingScale Up
EvolvingRegulatoryGuidance
Challenges
Oncology
>1400 >400
Neurological Disorders
>300
Genetic Disorders
>350
Others
Therapeutic areas
Adenovirus20%
Retrovirus18%
Plasmid DNA17%
*Adeno-associated virus
AAV*8%
Lentivirus7%
Others
VectorsAdenovirus
20%
Retrovirus18%
Plasmid DNA17%
*Adeno-associated virus
AAV*8%
Lentivirus7%
Others
Vectors
Scene 2
Major Key facts
in Gene Therapies
Cell with amutated gene Production of a
mutated proteinDiseases
Gene Therapy can correct these mutations
How does gene therapy
work ?Scene 3
By using CRISPR/CAS9
8,659
Mutated cell Identification of themutation responsible
for the diseaseCreation of a strand of guide RNA
that matches the mutated DNA sequence
Cas9 cuts, nicks or targets the affected sequence The Guide RNA identifies the mutated DNA
Guide RNA
Cas9
Addition ofTarget gene
DNA
Non-HomologousEnd-Joining
Gene knockoutPrime editingBase substitution
Adenine/Cytosine
base editorRT enzyme
Gene replacement Gene repair Gene silence
NONINTEGRATING VIRUSES INTEGRATING VIRUSES ONCOLYTIC VIRUSESNONINTEGRATING VIRUSES INTEGRATING VIRUSES ONCOLYTIC VIRUSES
By using Viral Vectors
The great story ofGene Therapy
Virus entersin the cell
Conversioninto DNA
Functionalprotein
expressed
DNA isintegrated into nuclear
genome
Adeno-associated virus(AAV)
Therapeutic DNA
Therapeutic DNA
Oncolytic virus
Lentivirus
TherapeuticRNA
Virus entersin the cell
Endosomebreaks down
Functionalprotein
expressedVirus bindsto the cellnucleus
Virus preferentiallyinfects tumor cells
Virus replicatewithin the cell
Tumor Lysis
IN VIVO
EX VIVO