INTERFERENCIA DE ARN ESPECIFICO DE ALELOS

• Main Authors: ZAMORE, PHILLIP, D, XU, ZUOSHANG
• Format: Patent
• Language: Spanish
• Published: 05.03.2010
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPIRITS; VINEGAR; WINE

Un procedimiento ex vivo para inhibir selectivamente la expresión de un alelo objetivo mutante de un gen SOD1 en una célula que comprende alelos de tipo salvaje y mutantes del gen, en donde el alelo objetivo comprende una mutación puntual correlacionada con la esclerosis lateral amiotrófica, el procedimiento comprende administrar a la célula un siARN específico para la mutación puntual de tal modo que ocurre la interferencia de ARN específica de alelos del alelo objetivo mutante y se preserva la expresión del alelo de tipo salvaje, en donde el siARN es apareado completamente con un mARN mutante codificado por el alelo mutante pero forma un mal apareamiento de un solo nucleótido con un mARN de tipo salvaje codificado por el alelo de tipo salvaje. Human diseases caused by dominant, gain-of-function mutations develop in heterozygotes bearing one mutant and one wild-type copy of a gene. Because the wild-type gene often performs important functions, whereas the mutant gene is toxic, any therapeutic strategy must selectively inhibit the mutant while retaining wild-type gene expression. The present invention includes methods of specifically inhibiting the expression of a mutant allele, while preserving the expression of a co-expressed wild-type allele using RNAi, a therapeutic strategy for treating genetic disorders associated with dominant, gain-of-function gene mutations. The invention also includes small interfering RNAs (siRNAs) and small hairpin RNAs (shRNAs) that selectively suppress mutant, but not wild-type, expression of copper zinc superoxide dismutase (SOD1), which causes inherited amyotrophic lateral sclerosis (ALS).