(c) 2008 Elsevier Ltd. All rights reserved.”
“Leber’s congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium-specific 65-kDa protein gene (RPE65). We investigated the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) (ClinicalTrials.gov number, NCT00516477). Three patients with LCA2 had an acceptable local and systemic adverse-event profile after delivery LY2874455 research buy of AAV2.hPPE65v2. Each patient had a modest

improvement in measures of retinal function on subjective tests of visual acuity. In one patient, an asymptomatic

macular hole developed, and although the occurrence was considered to be an adverse event, the patient had some return of retinal function. Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA.”
“The tri-frame model gives mathematical expression to the transcription and translation processes, and considers all three reading frames GSK1120212 purchase (RFs). RNA polymerases transcribe DNA in single nucleotide increments, but ribosomes translate mRNA in pairings of three (triplets or codons). The set of triplets in the mRNA, starting with the initiation codon (usually AUG) defines the open reading frame (ORF). Since ribosomes do not always translocate selleck three nucleotide positions, two additional RFs are accessible. The -1 RF and the +1 RF are triplet pairings of the mRNA, which are accessed by shifting one nucleotide position in the 5′ and 3′ directions, respectively. Transcription is modeled as a linear operator that maps the initial codons in all three frames into other codon sets to account for possible transcriptional errors. Translational errors (missense

errors) originate from misacylation of tRNAs and misreading of aa-tRNAs by the ribosome. Translation is modeled as a linear mapping from codons into aa-tRNA species, which includes misreading errors. A final transformation from aa-tRNA species into amino acids provides the probability distributions of possible amino acids into which the codons in all three frames could be translated. An important element of the tri-frame model is the ribosomal occupancy probabihty. It is a vector in R 3 that gives the probability to find the ribosome in the ORF, -1 or +1 RF at each codon position. The sequence of vectors, from the first to the final codon position, gives a history of ribosome frameshifting. The model is powerful: it provides explicit expressions for (1) yield of error-free protein, (2) fraction of prematurely terminated polypeptides, (3) number of transcription errors, (4) number of translation errors and (5) mutations due to frameshifting.