医学遗传学课件：11、Chapter 13 遗传病的治疗

1、http:/ 51 : DMD exon 51 skippingSpinraza : spinal muscular atrophy “Soon there will be no disease called breast cancer,” says Draghia-Akli. Instead, the catch-all term will be replaced by “a large number of rare diseases, each of which causes malignant growth in breast tissue and requires individual

2、 treatment”.遗传诊断产前诊断症状前筛查DiversionDepletionLDL apheresis 分离术分离术cholestyramine消胆氨消胆氨InhibitionStatins他汀他汀GBA合成酶活性部位特异的分子伴侣治疗活性部位特异的分子伴侣治疗Active-Site-Specific Chaperone therapy1-deoxy-galactonojirimycin (DGJ) for FabryN-nonyl-deoxynojirimycin (NN-DNJ) for GaucherVX-770G551D耳毒性耳毒性, 肾毒性肾毒性,神经肌肉阻断神经肌肉阻断,

3、 变态反应变态反应Antisense-induced exon skippingLancet 2008; 371: 212033Figure 1. People unaffected by SMA possess two SMN genes; SMN1 (green rectangle) produces all the functional SMN protein required for a healthy nervous system, while SMN2 (blue rectangle) only produces a fraction of that (top left). SMN

4、-AS1 (red oval) is a naturally occurring molecule in the body that restricts the amount of SMN protein made from both SMN genes. SMA patients lack a functioning SMN1 gene and rely solely on SMN2 for the production of SMN protein, meaning that they have much lower levels of functional SMN Protein (to

5、p right).Figure 2. Spinraza (purple rectangle) is an antisense oligonucleotide (ASO) that specifically recognises the messenger RNA (mRNA) produced from the SMN2 gene (top left). The SMN2 mRNA is processed in a different manner when Spinraza is present, resulting in the production of more functional

6、 SMN protein from this backup SMN gene. The new therapeutic strategy identified by the Sumner laboratory uses an ASO to remove the SMN-AS1 molecule from the SMN2 gene, allowing the gene to produce greater quantities of mRNA (top right). This gives Spinraza more material to work with, and produces la

7、rger amounts of functional SMN protein than when Spinraza is administered on its own.GOF: gain of functionLOF: loss of function离体离体 ex vivo在体在体 in vivoViral genometransgene基因转移的工具基因转移的工具反转录病毒反转录病毒载体载体HSV病毒病毒载体载体AAV病毒病毒载体载体RNA病毒病毒载体载体腺病毒载体腺病毒载体痘病毒痘病毒载体载体EBV病毒病毒载体载体病毒载体的种类病毒载体的种类1 1、利用病毒天然的感染性进入细胞，转导效率高；、利用病毒天然的感染性进入细胞，转导效率高；2 2、复杂的装配过程由细胞完成；、复杂的装配过程由细胞完成；3 3、不同的病毒载体具有不同的表达特点。、不同的病毒载体具有不同的表达特点。存在的问题