Editing Missense mutation (section)

=== Genetic engineering and drug-based interventions  ===
More recently, research has explored the use of [[genetic engineering]]<ref name="Hou_2024">{{cite journal | vauthors = Hou Y, Zhang W, McGilvray PT, Sobczyk M, Wang T, Weng SH, Huff A, Huang S, Pena N, Katanski CD, Pan T | title = Engineered mischarged transfer RNAs for correcting pathogenic missense mutations | journal = Molecular Therapy | volume = 32 | issue = 2 | pages = 352–371 | date = February 2024 | pmid = 38104240 | pmc = 10861979 | doi = 10.1016/j.ymthe.2023.12.014 }}</ref> and pharmaceuticals as potential treatments.<ref name="Striessnig_2021">{{cite journal | vauthors = Striessnig J | title = Voltage-Gated Ca<sup>2+</sup>-Channel α1-Subunit <i>de novo</i> Missense Mutations: Gain or Loss of Function - Implications for Potential Therapies | journal = Frontiers in Synaptic Neuroscience | volume = 13 | pages = 634760 | date = 2021-03-03 | pmid = 33746731 | pmc = 7966529 | doi = 10.3389/fnsyn.2021.634760 | doi-access = free }}</ref><ref name="Schulz-Heddergott_2018">{{cite journal | vauthors = Schulz-Heddergott R, Moll UM | title = Gain-of-Function (GOF) Mutant p53 as Actionable Therapeutic Target | journal = Cancers | volume = 10 | issue = 6 | pages = 188 | date = June 2018 | pmid = 29875343 | pmc = 6025530 | doi = 10.3390/cancers10060188 | doi-access = free }}</ref> tRNA therapies have emerged in research studies as a potential missense mutation treatment, following evidence supporting their use in nonsense mutation correction.<ref name="Albers_2021">{{cite journal | vauthors = Albers S, Beckert B, Matthies MC, Mandava CS, Schuster R, Seuring C, Riedner M, Sanyal S, Torda AE, Wilson DN, Ignatova Z | title = Repurposing tRNAs for nonsense suppression | journal = Nature Communications | volume = 12 | issue = 1 | pages = 3850 | date = June 2021 | pmid = 34158503 | pmc = 8219837 | doi = 10.1038/s41467-021-24076-x | bibcode = 2021NatCo..12.3850A }}</ref> Missense-correcting tRNAs are engineered to identify the mutated codon, but carry the correct charged amino acid which is inserted into the nascent protein.<ref name="Hou_2024" />   

Pharmaceuticals that target specific proteins affected by missense mutations have also shown therapeutic potential.<ref name="Striessnig_2021" /><ref name="Schulz-Heddergott_2018" /> Pharmaceutical studies have particularly focused on targeting the p53 mutant protein and Ca<sup>2+</sup> channel abnormalities, both caused by gain of function missense mutations due to their high prevalence in a number of cancers and genetic diseases respectively.<ref name="Schulz-Heddergott_2018" /><ref name="Albers_2021" /> In cystic fibrosis, most commonly caused by missense mutations,<ref>{{Cite journal |last=Serre |first=J.L. |last2=Mornet |first2=E. |last3=Simon-Bouy |first3=B. |last4=Boué |first4=J. |last5=Boué |first5=A. |date=2017-08-11 |title=General Cystic Fibrosis Mutations Are Usually Missense Mutations Affecting Two Specific Protein Domains and Associated with a Specific RFLP Marker Haplotype |url=https://karger.com/ejd/article-abstract/1/4/287/121582/General-Cystic-Fibrosis-Mutations-Are-Usually?redirectedFrom=fulltext |journal=European Journal of Human Genetics |volume=1 |issue=4 |pages=287–295 |doi=10.1159/000472426 |issn=1018-4813|url-access=subscription }}</ref> drugs known as modulators target the defective Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein.<ref>{{Cite journal |last=Edmondson |first=Claire |last2=Davies |first2=Jane C. |date=2016-05-01 |title=Current and future treatment options for cystic fibrosis lung disease: latest evidence and clinical implications |url=https://journals.sagepub.com/doi/10.1177/2040622316641352 |journal=Therapeutic Advances in Chronic Disease |language=en |volume=7 |issue=3 |pages=170–183 |doi=10.1177/2040622316641352 |issn=2040-6223 |pmc=4907071 |pmid=27347364}}</ref> For example, to reduce the defects caused by class III CFTR mutations, Ivacaftor, part of the modulator Kalydeco, forces the chloride channel to remain in an open position.<ref name=":12">{{Cite web |title=CFTR Modulator Therapies {{!}} Cystic Fibrosis Foundation |url=https://www.cff.org/managing-cf/cftr-modulator-therapies |access-date=2025-04-01 |website=www.cff.org |language=en}}</ref>