Table 1

Comparative analysis of protein replacement therapy, gene therapy and mRNA therapy for the treatment of genetic metabolic diseases

Protein replacement therapyGene therapymRNA-based therapy
Administration frequencyDaily to weeklySingle shotWeekly to monthly
ImmunogenicityAntidrug antibodies with chronic administrationsVector immunogenicity prevents readministration.Based on deimmunised mRNAs. Unknown long-term immunogenicity.
GenotoxicityNoneLow riskNone
Dose controlHighLow due to single shotHigh
Intracellular targetsDepends on a targeting moietyFeasibleFeasible
Therapeutic actionRapid (hourshour)Delayed (3–5 days)Rapid (hourshour)
Applicable to sporadic presentationsYesNo, but effective in preventing new symptomsYes
Relative production costHighHighLow
‘Advanced Therapy Medicinal Products’ regulation requiredNoYesNo