caa a22 4500 445860995 CHVBK 20180317145443.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s00439-011-0995-8 doi (NATIONALLICENCE)springer-10.1007/s00439-011-0995-8 Seyhan Attila Pfizer Inc., Translational Immunology, Inflammation and Immunology, 200 Cambridgepark Drive, 02140, Cambridge, MA, USA aut RNAi: a potential new class of therapeutic for human genetic disease [Elektronische Daten] [Attila Seyhan] Dominant negative genetic disorders, in which a mutant allele of a gene causes disease in the presence of a second, normal copy, have been challenging since there is no cure and treatments are only to alleviate the symptoms. Current therapies involving pharmacological and biological drugs are not suitable to target mutant genes selectively due to structural indifference of the normal variant of their targets from the disease-causing mutant ones. In instances when the target contains single nucleotide polymorphism (SNP), whether it is an enzyme or structural or receptor protein are not ideal for treatment using conventional drugs due to their lack of selectivity. Therefore, there is a need to develop new approaches to accelerate targeting these previously inaccessible targets by classical therapeutics. Although there is a cooling trend by the pharmaceutical industry for the potential of RNA interference (RNAi), RNAi and other RNA targeting drugs (antisense, ribozyme, etc.) still hold their promise as the only drugs that provide an opportunity to target genes with SNP mutations found in dominant negative disorders, genes specific to pathogenic tumor cells, and genes that are critical for mediating the pathology of various other diseases. Because of its exquisite specificity and potency, RNAi has attracted a considerable interest as a new class of therapeutic for genetic diseases including amyotrophic lateral sclerosis, Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD), spinocerebellar ataxia, dominant muscular dystrophies, and cancer. In this review, progress and challenges in developing RNAi therapeutics for genetic diseases will be discussed. Springer-Verlag, 2011 Human Genetics Springer-Verlag 130/5(2011-11-01), 583-605 0340-6717 130:5<583 2011 130 439 https://doi.org/10.1007/s00439-011-0995-8 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-0995-8 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Seyhan Attila Pfizer Inc., Translational Immunology, Inflammation and Immunology, 200 Cambridgepark Drive, 02140, Cambridge, MA, USA aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 130/5(2011-11-01), 583-605 0340-6717 130:5<583 2011 130 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer