|Gene therapy||Gene therapy involves replacing the mutant copy of the gene with a wild-type functional protein.|
|Gene editing||CRISPR/Cas9 is a gene-editing strategy where only the mutated sequence of a mutant gene is edited and thereby corrected for proper function of the protein.|
|Gene correction in iPSCs||Using specialized induced pluripotent stem cells (iPSCs), CRISPR/Cas9 editing allows the correction of the gene within iPSCs increasing effectiveness of the technique.|
|Modulator Therapies--using differing mechanisms of action-||Modulators can be either potentiators, correctors [pharmacological chaperones & proteostasis regulators], stabilizers, or amplifiers.|
|Modulators are pharmaceutical agents that targets specific defects in the mutant protein and/or modulate the intracellular environment.|
• Modulators target protein errors that occur post-transcriptionally, such as during protein folding, anterograde trafficking and further assist protein function and signaling following protein expression.
○ Correctors improve intracellular processing of misfolded proteins and increase plasma membrane expression.
○ Potentiators and stabilizers help the misfolded protein once expressed. Combination therapies with different mechanisms of actions, show greater efficacy.
• Proteostasis regulators improve the overall quality of the proteostasis network within a cell.
○ Regulators can be designed to increase the function and availability of molecular chaperones, and consequently promote protein folding and/or reduce misfolding.
○ Regulators targeting the ER quality control can enhance the elimination of non-native conformations of polypeptides.
|Stem cell therapy||Stem cell therapy is a tailored approach which is easy to proliferate and modify. It can further be coupled with CIRSPR/Cas9 and correct cells to a WT phenotype in the correct cell-line.|
|Antisense-oligonucleotide-mediated therapy||Single-stranded synthetic RNA-like molecules known as antisense oligonucleotides (ASOs) selectively change gene expression.|
|Non-viral vectors||Non-viral vectors have the ability to pack and deliver bulky DNA molecules with liposomal vectors.|
|mRNA-mediated therapy||Wild-type nucleotide sequence is targeted to the cell and has the ability to encode wild-type protein.|
|Proteasome inhibitors||Inhibition of proteasome, a unique proteolytic complex, prevents degradation of ubiquitinated proteins tagged for ERAD.|