Gene Therapy - Successess?

[molecule2005]

Great information here on Gene Therapy Cebe and Frank

I have heard of some more successes recently on gene therapy but I forgot what they were...

[Cebe]

Originally Posted by Frank

Hi Cebe,

thanks for your input! You seem to know a lot about this subject, do you work in this field?

Hi Frank,

... for 16 years!!!

[Frank]

This study used nanoparticles to deliver RNA molecules body wide to treat mdx mice ("Duchenne mice").

Cationic PMMA Nanoparticles Bind and Deliver Antisense Oligoribonucleotides Allowing Restoration of Dystrophin Expression in the mdx Mouse.
Rimessi P, Sabatelli P, Fabris M, Braghetta P, Bassi E, Spitali P, Vattemi G, Tomelleri G, Mari L, Perrone D, Medici A, Neri M, Bovolenta M, Martoni E, Maraldi NM, Gualandi F, Merlini L, Ballestri M, Tondelli L, Sparnacci K, Bonaldo P, Caputo A, Laus M, Ferlini A.

1Department of Experimental and Diagnostic Medicine, Section of Medical Genetics, University of Ferrara, Ferrara, Italy.

For subsets of Duchenne muscular dystrophy (DMD) mutations, antisense oligoribonucleotide (AON)-mediated exon skipping has proven to be efficacious in restoring the expression of dystrophin protein. In the mdx murine model systemic delivery of AON, recognizing the splice donor of dystrophin exon 23, has shown proof of concept. Here, we show that using cationic polymethylmethacrylate (PMMA) (marked as T1) nanoparticles loaded with a low dose of 2'-O-methyl-phosphorothioate (2'OMePS) AON delivered by weekly intraperitoneal (IP) injection (0.9 mg/kg/week), could restore dystrophin expression in body-wide striated muscles. Delivery of an identical dose of naked AON did not result in detectable dystrophin expression. Transcription, western, and immunohistochemical analysis showed increased levels of dystrophin transcript and protein, and correct localization at the sarcolemma. This study shows that T1 nanoparticles have the capacity to bind and convoy AONs in body-wide muscle tissues and to reduce the dose required for dystrophin rescue. By immunofluorescence and electron microscopy studies, we highlighted the diffusion pathways of this compound. This nonviral approach may valuably improve the therapeutic usage of AONs in DMD as well as the delivery of RNA molecules with many implications in both basic research and medicine.Molecular Therapy (2009); doi:10.1038/mt.2009.8.

[Jon Moulton]

Hi Frank,

That citation discusses experiments using 2'-O-methyl phosphorothioate oligos, a modified form of RNA that does not code for protein. Instead, the oligos bind to pre-mRNA and redirect splicing, leading to excision of targeted exons. Some would say this is not "gene therapy" as it causes no change in DNA. However, it is a very promising therapeutic strategy for Duchenne muscular dystrophy. The 2'-O-methyl phosphorothioate oligos are in clinical trials for DMD, as are another steric-blocking antisense type, Morpholino oligos.

[asaroj27]

Hello
The scientists are allowed to perform only somatic gene therapy and the biggest limitation of this therapy is that it is not effective for long time because we don’t know the Ori for most of the gene. So when we get the good knowledge about the Ori then we can use, gene therapy to treat any genetic disorder.If you want to know more regarding this you can ask.
Thank you

[here444]

you guys are smart

[Jon Moulton]

Here we go...

Kinali M, Arechavala-Gomeza V, Feng L, Cirak S, Hunt D, Adkin C, Guglieri M, Ashton E, Abbs S, Nihoyannopoulos P, Garralda ME, Rutherford M, McCulley C, Popplewell L, Graham IR, Dickson G, Wood MJ, Wells DJ, Wilton SD, Kole R, Straub V, Bushby K, Sewry C, Morgan JE, Muntoni F. [Only registered users see links. ] Lancet Neurol. 2009 Oct;8(10):918-28. Epub 2009 Aug 25.

[Only registered users see links. ]

Note: this is an open-access paper but you must register with Lancet Neurology for access. There is a link to Lancet Neurology on the PubMed page at the upper right side.