醫(yī)學遺傳學課件：11、Chapter 13 遺傳病的治療

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”.遺傳診斷產(chǎn)前診斷癥狀前篩查DiversionDepletionLDL apheresis 分離術分離術cholestyramine消膽氨消膽氨InhibitionStatins他汀他汀GBA合成酶活性部位特異的分子伴侶治療活性部位特異的分子伴侶治療Active-Site-Specific Chaperone therapy1-deoxy-galactonojirimycin (DGJ) for FabryN-nonyl-deoxynojirimycin (NN-DNJ) for GaucherVX-770G551D耳毒性耳毒性, 腎毒性腎毒性,神經(jīng)肌肉阻斷神經(jīng)肌肉阻斷,

3、 變態(tài)反應變態(tài)反應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離體離體 ex vivo在體在體 in vivoViral genometransgene基因轉(zhuǎn)移的工具基因轉(zhuǎn)移的工具反轉(zhuǎn)錄病毒反轉(zhuǎn)錄病毒載體載體HSV病毒病毒載體載體AAV病毒病毒載體載體RNA病毒病毒載體載體腺病毒載體腺病毒載體痘病毒痘病毒載體載體EBV病毒病毒載體載體病毒載體的種類病毒載體的種類1 1、利用病毒天然的感染性進入細胞，轉(zhuǎn)導效率高；、利用病毒天然的感染性進入細胞，轉(zhuǎn)導效率高；2 2、復雜的裝配過程由細胞完成；、復雜的裝配過程由細胞完成；3 3、不同的病毒載體具有不同的表達特點。、不同的病毒載體具有不同的表達特點。存在的問題