Genes suppression

J. P., SozEN, M. A., Baron, A., Zeng, C., Frigkson, P. F., Hooper, J. E., Drabkin, H. a. The TRC8 hereditary kidney cancer gene suppresses growth and functions with VHL in a common pathway. Oncogene 2002, 21, 3507— 3516. 

Sidorova, J. and Breeden, L. (1999) The MSN and NHP6A genes suppress SWI6 defects in Saccharomyces cerevisiae. Genetics 151, 45-55. 

Synthesis, purification and annealing of siRNA by industrial chemical processes, for direct use in gene suppression experiments, is becoming increasingly popular. The characteristics of those sequences that constitute the most inhibitory siRNAs are unresolved it is not currently possible to predict the degree of gene suppression a particular siRNA will produce. It is recommended that the siRNA target site be located >100 nucleotides from the initiation codon and >50 nucleotides from the termination codon (Sui et al., 2002). For optimal siRNA secondary structure, the GC ratio should ideally be between 45% and 55%. It is... 

Yin JY, Ma ZY, Selliah N, Shivers DK, Cron RQ, Finkel TH (2006) Effective gene suppression using small interfering RNA in hard-to-transfect human T cells. J Immunol Meth 312 1-11... 

Ruan, S., Tate, C., Lee, J. J., Ritter, T., Rolls, J. K. and Shellito, J. E. (2002). Local delivery of the viral interleukin-10 gene suppresses tissue inflammation in murine Pneumocystis carinii infection. Infect. Immun. 70,... 

Higuchi, N., Maruyama, H., Kuroda, T., Kameda, S., lino, N., Kawachi, H., Nishikawa, Y., Hanawa, H., Tahara, H., Miyazaki, J. and Gejyo, F. (2003). Hydrodynamics-based delivery of the viral interleukin-10 gene suppresses experimental crescentic glomerulonephritis in Wistar-Kyoto rats. Gene Ther. 10, 1297-1310. 

Kariko K, Bhuyan P, Capodici J, Weissman D. Small interfering RNAs mediate sequence-independent gene suppression and induce immune activation by signaling through Toll-like receptor 3. J Immunol 2004 172(ll) 6545-9. 

Itokawa M, Yamada K, Yoshitsugu K, Toyota T, Suga T, et al. 2003. A microsatellite repeat in the promoter of the N-methyl-D-aspartate receptor 2A subunit (GRIN2A) gene suppresses transcriptional activity and correlates with chronic outcome in schizophrenia. Pharmacogenetics 13 271-278. 

These genes were called tumor suppressor genes because the transferred genes suppressed growth and/or tumorigenicity. 

RNA interference (RNAi) is a phenomenon comprising the ability of double-stranded RNA (dsRNA) molecules to stimulate eukaryotic gene suppression in a sequence-specific manner. This article will first outline the essential molecular biological principles of RNAi and then focus on RNAi s practical applications. It will explain how dsRNAs can be delivered to or expressed inside mammalian cells, and what considerations are usually taken into account when choosing various RNAi approaches. In addition, the discussion describes how RNAi can be applied in the drug target discovery and validation process, and what potentials RNAi hold as a therapeutic modality. 

By reversing the polarity of the DNA strands, the opposite strand will be transcribed and a complementary or antisense RNA will be produced. When antisense RNA was introduced either in vitro (27) or in vivo (28), the presence of the antisense RNA inhibited the expression of the normal RNA transcript produced by the resident gene. Suppression of RNA translation by antisense RNA may be due to the formation of an RNA heteroduplex between the two complementary RNA strands thus blocking the attachment of ribosomes. An example of this application in the context of the Adh example would be the construction of a chimeric gene containing the antisense sequence for Adh linked with a female-specific promoter. Thus, Adh activity would be eliminated from females and make them lethally sensitive to treatment with ethanol. 

Because the cellular processing of mi-RNAs and siRNAs converges and achieves similar functional outcomes (gene suppression), the miRNA class of small regulatory RNAs serves as a potential source of information regarding characteristics that are essential for siRNA functionality. Mi-croRNAs have apparently been part of the cellular defense or regulatory mechanism of plants and metazoans for much of their evolutionary history, and therefore, as a result of selection pressure, miRNAs might... 

This gene suppression allowed administration of the anti-angiogenic molecule thrombospondin-1 (TSPl) to significantly inhibit tumor growth. These and other in... 

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