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Biotech / Medical : Unquoted Biotechs -- Ignore unavailable to you. Want to Upgrade?

To: Mike McFarland who wrote (31)	1/15/2002 9:50:48 PM
From: SnowShredder	Read Replies (1) \| Respond to of 253

Hi Mike, I'm no GT expert, but I'll my 2 worthless cents anyways >gg< In the article on pg 51, the author mentions "(rAAV)will probably be the vector of choice for clinical applications in CF." From their website...<snip> "PTMs should be deliverable by almost any means used in gene therapy. The binding domain and splice site of a PTM need only be 60 to 80 nucleotides in length. If the PTM is designed to deliver a short region consisting of a stop codon or a peptide, the entire PTM may be under 120 nucleotides, which can be synthesized. This would allow the PTM to be delivered by methods employed to deliver anti-sense oligonucleotides. Most likely, the mode of delivery will be dictated by the total length of the PTM and the term of expression desired to be produced by the PTM trans-spliced therapeutic gene. " <snip> ...<snip> "Antisense oligomers Antisense oligomers can be targeted to pre-mRNA splice sites to modulate splicing patterns. The number of diseases amenable to this method is limited. This approach is appropriate for repairing mutations that produce aberrant splicing patterns, such as some forms of beta-thalasemia. Trans-splicing ribozymes Ribozymes have been successfully employed to correct mRNAs, replacing mutations located 3’ to the ribozyme splice site. In some applications, efficiencies approaching 50% have been reported. Additionally, treatment for gain of function mutations can be envisioned. This would include mutations in cancer suppressor genes (p53) and trinucleotide repeat diseases (fragile X, Huntington disease and myotonic dystrophy). With this level of repair, many different genetic disease phenotypes could be effectively treated. However, after years of study and development, ribozyme target specificity remains poor. The lack of specificity has been attributed to the short target binding domain of the trans-splicing ribozyme, which is only 6 nucleotides in length. It remains to be seen if this lack of specificity introduces new problems. Spliceosome Mediated RNA Trans-splicing -SMaRT Like trans-splicing ribozymes, SMaRT technology can be applied to repair large portions of expressed mutant genes, in this case at the pre-mRNA level. SMaRT technology offers several potential advantages over ribozymes. 1. SMaRT can effect a repair either 5¹ or 3¹ to a mutation 2. A double trans-splicing PTM may be constructed to replace only a single mutant exon, greatly reducing the size of the gene therapeutic that must be delivered to the cell 3. Target specificity may be much better with SMaRT PTMs than with trans-splicing ribozymes, as the PTM binding domain can be any length or composition necessary to confer the required specificity. The binding domain of a ribozyme must meet the demands of both conferring specificity to target and forming part of the catalytic structure of the ribozyme. Unfortunately to date, the ribozyme target binding domain (internal guide sequence) is limited to 6 nucleotides in length. "<snip> I think they have some very interesting stuff...probably worth keeping an eye on...bwdik? Best of Luck, SS