gene therapy
Introduction
Targeting of genetically engineered genes to specific cells may be possible using nanoparticles engineered to bind to cell surface receptors specific for particular cell types. With choice of appropriate receptor, the gene is internalized into the target cell.
This approach has been used to introduce a mutant form of raf into endothelial cells comprising new blood vessels. The mutant raf causes death of endothelial cells, disrupting blood supply to the tumor. This treatment apparently stopped cancer growth abruptly & caused regression of tumors in rats.[1]
An adenovirus has been used to introduce 2 genes into mice treated with streptozocin to destroy pancreatic islet cells. These 2 genes neurod & Btc stimulated formation of functional islet cells throught the liver. Insulin, glucagon & somatostatin producing cells were formed. Treatment conferred normal control of blood glucose.[2]
An adenovirus vector has been used to introduce factor IX into 7 patients with hemophilia B. 4 of 7 patients able to discontinue prophylactic factor IX (Benefix vs Aprolix) with beneficial effects in all 7 patients up to 3 years. The main complication in this approach is liver toxicity associated with the adenovirus vector[8]
Revertant mosaicism correcting disease phenotype due to multiple correcting second-site mutations may have implications for gene therapy.[3]
PTC124, an oral agent, may correct defects resulting from nonsense mutations that lead to a premature termination codon[4]
Convection-enhanced delivery may have potential of delivering candidate genes to otherwise inaccessible regions of the brain
lentivirus vector might promote better integration of functional genes; used successfully for
- delivering functional beta-globin gene to hematopoietic cells of 18 year old man with beta-thalassemia[6]
- into CD34+ bone marrow enriched cells in 13 year old boy with sickle cell disease[9]
- for introducing genes enabling continuous production of dopamine into the putamen of patients with Parkinson's disease[7]
More general terms
More specific terms
- beremagene geperpavec-svdt (Vyjuvek)
- delandistrogene moxeparvovec-rokl (Elevidys)
- etranacogene dezaparvovec-drlb (Hemgenix)
- gene therapy for Parkinson's disease
- lenadogene nolparvovec (Lumevoq)
- valoctocogene roxaparvovec-rvox (Rocktavian)
- voretigene neparvovec-rzyl (Luxturna)
Additional terms
References
- ↑ 1.0 1.1 Journal Watch 22(15):116, 2002 Hood JD et al, Science 296:2404, 2002
- ↑ 2.0 2.1 Journal Watch 23(13):108, 2003 Kojima et al, Nat Med 9:596, 2003
- ↑ 3.0 3.1 Pasmooij AM, Pas HH, Bolling MC, Jonkman MF. Revertant mosaicism in junctional epidermolysis bullosa due to multiple correcting second-site mutations in LAMB3. J Clin Invest. 2007 May;117(5):1240-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17476356
- ↑ 4.0 4.1 Welch EM et al, PTC124 targets genetic disorders caused by nonsense mutations Nature 2007, 447:87 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17450125
Schmitz A and Famulok M Chemical biology: Ignore the nonsense. Nature 2007, 447:42 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17450128 - ↑ UCSF Medical Center News, April 14, 2009 Researchers Develop New Gene Therapy Technique for Brain Disorders http://www.ucsfhealth.org/adult/health_library/news/2009/04/121437.html
- ↑ 6.0 6.1 Cavazzana-Calvo M et al. Transfusion independence and HMGA2 activation after gene therapy of human-beta-thalassaemia. Nature 2010 Sep 16; 467:318. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20844535 <Internet> http://dx.doi.org/10.1038/nature09328
Persons DA. Gene therapy: Targeting beta-thalassaemia. Nature 2010 Sep 16; 467:277 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20844523 - ↑ 7.0 7.1 Palfi S et al Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial. The Lancet, Early Online Publication, 10 January 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24412048 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961939-X/abstract
Stoessl AJ Gene therapy for Parkinson's disease: a step closer? The Lancet, Early Online Publication, 10 January 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24412047 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2962108-X/fulltext - ↑ 8.0 8.1 Nathwani AC et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med 2014 Nov 20; 371:1999 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25409372 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1407309
- ↑ 9.0 9.1 Ribeil JA, Hacein-Bey-Abina S, Payen E et al. Gene therapy in a patient with sickle cell disease. N Engl J Med 2017 Mar 2; 376:848 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28249145 <Internet> http://www.nejm.org/doi/10.1056/NEJMoa1609677