Many human cancers result when a normal gene mutates and leads to uncontrolled g

Question

Many human cancers result when a normal gene mutates and leads to uncontrolled growth (a tumor). Genes that cause cancer when they mutates are called oncogenes. Chemotherapy is effective against many tumors because it targets rapidly dividing cells and kills them. Unfortunately, chemotherapy has many side effects, such as hair loss or nausea, because it also kills many of our normal cells that are rapidly dividing, such as in the hair follicles or stomach lining.

Many scientists and large pharmaceutical companies are excited about the prospects of exploiting the RNAi pathways to selectively inhibit oncogenes in life-threatening tumors. Explain in very general terms how gene-silencing therapy might work to treat cancer and why this type of therapy would have fewer side effects than chemotherapy.

Explanation / Answer

RNAi or antisense RNA targets specific mRNAs and inhibit their expression. Antisense oligonucleotides hybridize with target mRNA sequences. For treatment of cancers, phosphodiester oligonucleotide directed against cancer/tumor specific genes was successully experimented. Phospho diester bond is highly susceptible to degradation. This finding led to development of phosphoorothioate chemistry, in which the oxygen in the phospho diester bond is replaced by sulfer atom in each internucleotide linkage. The phosphoorothioate antisense had shown broad ange of activity in preclinical studies.

Mechanism of RNAi silencing of genes: In mammals, double stranded RNAs longer than 30 nucleotides stimulates the activation of dsRNA-activated protein kinase. This enzyme induces non-specific inhibition of protien translation and leads to cell death. Synthetic RNAi that mimic Dicer cleavage products efficiently induce sequence-specific gene silencing, when transiently transfected into mammalian cells. Such RNAi specific for the tumor specific genes are introduced into the cancers, in which, the tumor specific gene expression is inhibited the RNA silencing.

Related Questions

Navigate

• Browse (All)
• Browse M
• Subjects

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.