Treatment Strategies of
Monogenic Diseases

DNA-Based Strategies

Different strategies are being utilized for the treatment of monogenic diseases. These include DNA and RNA-based approaches as well as protein and substrate-based therapies1,5


Substrate and protein-based therapies target the downstream consequence of gene mutations

DNA-based and some RNA-based strategies target the abnormality in the gene itself6–10

Protein Based Strategies:

Replace a deficient or abnormal protein

Enhance endogenous enzyme activity

Substrate Based Strategies:

Restrict consumption of offending substrate

Facilitate degradation or removal of toxic substrate

RNA Based Strategies:

Facilitate exon skipping 
and re-code premature termination codon

Alter gene expression or RNA processing

DNA Based Strategies:

Manipulate genes to prevent or treat a disease

Gene Therapy1


Personalized therapy


Blood–brain barrier represents a challenge

Immune response

Cellular toxicity

Potential oncogenesis

Technological limitations

Ethical issues

Examples of Potential Disease Targets

Retinal dystrophy

Spinal muscular dystrophy




Voretigene neparvovec-rzyl*

Voretigene neparvovec-rzyl*, the first approved in vivo gene therapy product in the U.S., is indicated for the treatment of children and adult patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy. Mutations in RPE65 block the visual cycle and impair vision. Treatment results in delivery of a normal copy of the RPE65 gene directly to retinal cells3