Correcting abnormal alternative splicing using SMARTTM Sample Clauses

Correcting abnormal alternative splicing using SMARTTM. With SMARTTM, a chimaeric mRNA is created by trans-splicing where the spliceosome catalyses the reaction between the 5’ splice site of a natural target pre-mRNA and the 3’ splice site of an exogenous delivered pre-trans-splicing molecules (PTM) RNA molecule (Xxxxx et al., 2007; Xxxxxxxxx et al., 1999). The reprogramming of tau pre-mRNA using spliceosome-mediated RNA trans- splicing (SMARTTM) can correct aberrant alternative splicing. SMARTTM corrects abnormal splicing at the RNA level such that the correct transcript is expressed and the mutant form of the transcript is down-regulated concurrently (Xxxxx et al., 2007). SMART adequately modulates exon 10 splicing of tau pre-mRNA. Using SMARTTM, exclusion of exon 10 was achieved with 30 % efficiency (Xxxxxxxxx- Xxxxxx et al., 2005) (Xxxxxxxxx-Xxxxxx et al., 2009). In the context of tauopathies with increased expression of tau exon 10 mRNA such as some FTDP-17 mutations, SMARTTM can be used to create a chimeric mature transcript to correct abnormal tau isoform ratio (Xxxxxxxxx-Xxxxxx et al., 2005). Treatment of diseases caused as a result of defective alternative splicing by directly interfering with the RNA requires the delivery of the PTM through viral vectors. This avoids the obstacles of the blood brain barrier as well as decreasing the possibility of side-effects (Xxxxx et al., 2007).
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