It is called Splicer and in animal models it reduces the production of the beta amyloid protein. Believed to be responsible for the pathology.Many diseases are caused by a malfunctioning protein, and strategies. To combat them aim to repair the damage and replace the function of the diseased protein in different ways. But there is another way: the protein can be modified just enough to make it less “toxic.” This is the goal of some bioengineering experts, creators of Splicer: it is a genetic editing technique, presented in the pages of Nature Communications. And aims, precisely, to modify the diseased proteins underlying various diseases. At the moment it has been tested in vivo on animal models of Alzheimer’s with encouraging results.
A new platform
Splicer – the authors explain – is an exon skipping platform: it is a strategy that aims to modify a protein by eliminating (more correctly skipping) a portion (exon) of the corresponding messenger RNA. The aim is to produce a protein deprived of the “sick” portion contained within the skipped exon. As explained by Pablo Perez-Pinera of the University of Illinois Urbana-Champaign, the individual in charge of the study: “If we succeed to neglect the component of the gene by the toxic alteration. The final protein may still contain enough ability to complete all its essential roles” .
Improving technologies
Exon skipping technologies already exist – such as antisense oligonucleotides. Used for example in ALS (amyotrophic lateral sclerosis) – but they are far from perfect and flexible. According to researchers, in fact, in some cases they can only be used on certain gene portions or are not entirely efficient in skipping exons.
Splicer would represent an advance, with the promise of improving the final result. To put it simply, the secret would be all in the new tool’s ability to act simultaneously on the beginning and end of each unwanted exon (in jargon acceptor and donor sites), the authors specify.
Evidence in Alzheimer’s models
Tested on cultured cells and in vivo on some animal models of Alzheimer’s . Splicer has shown that it works: it is able to reduce the formation of beta amyloid. The protein that is thought to be at the basis of the disease.
In this case, the part that is skipped is the one containing a sequence that favors the formation of beta amyloid starting from its precursor. Encoded by the App gene, linked to some familial forms of the disease.
Next steps
The authors state that Splicer is an effective and generally applicable tool. But whether the system can actually work is still too early to say. Experiments in animal models are promising. But there are still many steps to go before we can demonstrate its real efficacy, as well as safety and precision in humans. We should also do long-term animal studies and see if the disease progresses over time.”https://youtu.be/HANo__Z8K6s?si=WX41FfKJaqDFB_fk