Question

With regards to Spinal Muscular Atrophy and the Antisense.

1. The role of the protein targeted by the antisense [3pts]

2. The specific sequence of the mRNA targeted [3pts]

3. The specific sequence of your antisense molecule [3pts]

4. The specific amino acid sequence affected by binding of the antisense molecule [3pts]

5.Why you targeted that specific sequence [3pts]

6. Modifications made to the antisense molecule to enhance its resistance to RNAse H; if no modifications were done for your molecule, please discuss possible modifications that can be done. [3pts].

Answer 1

1. The protein targeted by antisense is SMN(survival motor neuron) protein.It plays important role in regulation of transcription, managing cellular traffic and regeneration of telomerase. Deficiency of this protein leads to waste of voluntary muscles.

2. The antisense targets a sequence in intron 7 of the SMN2 pre-mRNA.The sequence is: CAGCAUUAUGAAAGUGA

3.The antisense possess a sequence complementary to that in the mRNA. The sequence is: GUCGUAAUACUUUCACU

4. Gln-His-Tyr-Glu-Ser is the affected amino acid sequence.

5. This particular sequence is targeted because it leads to the splicing correction of SMN2 exon 7.

6. Antisense molecules can be modified by conjugating it with other moieties in order to produce improved antisense molecules.