Monogenic Diseases & Gene Therapy Approaches
This mapper identifies diseases caused by single-gene mutations and their corresponding gene therapy strategies:
- Gene Replacement: Deliver functional copies via viral vectors (AAV, lentiviral, adenoviral) to restore protein function
- RNA Interference: Silence disease-causing alleles using antisense oligonucleotides or siRNA (e.g., nusinersen for SMA)
- CRISPR/Base Editing: Correct mutations in-situ using genome editing (e.g., exagamglogene autotemcel for RPE65-LCA)
- Protein Replacement: Enzyme replacement therapy (ERT) for lysosomal storage diseases
Clinical trials count reflects active and completed studies from ClinicalTrials.gov.
Monogenic Diseases & Therapy Candidates
Sorted by clinical trial activity (most advanced first)
Showing 5 diseases
Hemophilia
Inheritance Pattern:
X-Linked Recessive
Clinical Trials:
15
Primary Genes
Genetic Testing / Biomarkers
• Factor VIII/IX activity assay
• FVIII/FIX gene sequencing
• aPTT (activated partial thromboplastin time)
FDA/EMA Approved Therapies
Valoctocogene roxaparvovec (Roctavian)
AAV5-mediated F8 gene therapy (Hemophilia A) (2024)
Mutations: All F8 mutations
Eteplirsen (Exondys51)
Antisense oligonucleotide for F8 exon-51 (2016)
Mutations: F8 exon-51 deletable
Mutation Stratification
• F8 mutations (>1800 known)
• F9 mutations (>1000 known)
Sickle Cell Disease
Inheritance Pattern:
Autosomal Recessive
Clinical Trials:
12
Primary Genes
Genetic Testing / Biomarkers
• HBB gene sequencing
• Hemoglobin electrophoresis
• Solubility test
FDA/EMA Approved Therapies
Exagamglogene autotemcel (Casgevy)
CRISPR base-editing ex vivo (2023)
Mutations: All SCD mutations
Frangakis—Bluebird Bio LentiGlobin
Lentiviral gene therapy (pending) (2023)
Mutations: βS/βS or βS/βC
Voxelotor (Oxbryta)
Hemoglobin S polymerization inhibitor (2019)
Mutations: All SCD mutations
Mutation Stratification
• βS/βS (homozygous)
• βS/βC (HbSC disease)
• βS/βThal (thalassemia variant)
Cystic Fibrosis
Inheritance Pattern:
Autosomal Recessive
Clinical Trials:
8
Primary Genes
Genetic Testing / Biomarkers
• CFTR sequencing
• Sweat chloride test
• Immunoreactive trypsinogen (IRT)
FDA/EMA Approved Therapies
Lumacaftor/Ivacaftor (Orkambi)
CFTR potentiator (2015)
Mutations: F508del/F508del
Elexacaftor/Tezacaftor/Ivacaftor (Trikafta)
CFTR corrector + potentiator (2019)
Mutations: Any with F508del
Mutation Stratification
• F508del (70% prevalence)
• G551D
• N1303K
• Other loss-of-function
Alpha-1 Antitrypsin Deficiency
Inheritance Pattern:
Autosomal Recessive
Clinical Trials:
4
Primary Genes
Genetic Testing / Biomarkers
• AAT serum level (<57 µM indicates deficiency)
• AAT phenotyping (PiZZ, PiMZ, etc.)
• SERPINA1 gene sequencing
FDA/EMA Approved Therapies
AAT augmentation therapy (IV infusion)
Protein replacement (purified human AAT) (1987)
Mutations: PiZZ, PiSZ
Mutation Stratification
• PiZZ (severe deficiency, ~55% normal levels)
• PiMZ (intermediate)
• PiSZ (intermediate)
Huntington Disease
Inheritance Pattern:
Autosomal Dominant
Clinical Trials:
4
Primary Genes
Genetic Testing / Biomarkers
• HTT CAG repeat length (>39 repeats diagnostic)
• MRI for basal ganglia atrophy
• HTT huntingtin protein levels
FDA/EMA Approved Therapies
Tominersen (IONIS-HTT-Rx)
Antisense oligonucleotide (HTT lowering) (Phase 3)
Mutations: All HTT mutations
Valbenazine (Ingrezza)
Symptomatic (VMAT2 inhibitor for chorea) (2016)
Mutations: All HTT mutations
Mutation Stratification
• CAG repeat: 40-49 (incomplete penetrance)
• CAG repeat: ≥50 (full penetrance)
• CAG repeat: >60 (juvenile onset)