Lo studio mostra la promessa per il trattamento di malattie genetiche in un mammifero durante lo sviluppo fetale nei primi tre mesi di gravidanza
A genetico il disturbo è una condizione o una malattia causata da cambiamenti o mutazioni anormali nel DNA di una persona nel gene. I nostri DNA provides the required code for making proteins which then perform most of the functions in our body. Even if one section of our DNA gets altered in some way, the protein associated with it can no longer carry out its normal function. Depending upon where this change happens either it can have a little or no effect or it might alter the cells so much that it could then lead to a genetico disorder or illness. Such changes are caused by errors in DNA replication (duplication) during growth, or environmental factors, lifestyle, smoking and exposure to radiation. Such disorders are passed on to the offspring and start to occur when the baby is developing in mother’s uterus and are therefore referred to as ‘birth defects’.
Birth defects can be minor or extremely severe and may affect appearance, function of an organ and some aspect of physical or mental development. Millions of children are born annually with serious genetico conditions. These defects can be detected during pregnancy as they are evident within the first three months of pregnancy when the organs are still forming. A technique called amniocentesis is available for detecting genetico abnormalities in the foetus by testing amniotic fluid extracted from the uterus. However, even with amniocentesis, treating them is not possible as no options are available to make any corrections before birth of the baby. Some of the defects are harmless and require no intervention but some others can be of serious nature and may require long-term treatment or even be fatal for the infant. Some defects can be corrected shortly after birth of the baby – example within a week’s time – but mostly it is too late for treatment.
Curare genetico condition in an unborn baby
For the first time the revolutionary gene editing technique has been used to cure a ‘genetico disorder’ in mice during foetal development in the uterus in a study by researchers at Carnegie Mellon University and Yale University. It is well established that during early development in the embryo (during first three months of a pregnancy) there are many stem cells (an undifferentiated cell type which can become any type of cell upon maturation) that are dividing at a fast rate. This is the pertinent time point where a genetico mutation if corrected would reduce the impact of the mutation on embryo-to-foetal development. There are chances that a severe genetico condition could even be cured and the baby is born without the unintended birth defects.
In questo studio pubblicato su Nature Communications researchers have used a peptide nucleic acid-based gene editing technique. This technique has been used before to treat beta thalassemia – a genetico blood disorder in which haemoglobin (HB) produced in the blood is reduced considerably which then affects normal oxygen supply to various parts of the body leading to severe abnormal consequences. In this technique, unique synthetic molecules called peptide nucleic acids (PNAs) (made of a combination of synthetic protein backbone with DNA and RNA) were created. A nanoparticle was then used to transport these PNA molecules along with “healthy and normal” donor DNA to the location of a genetico mutation. The complex of PNA and DNA identifies the designated mutation at a site, PNA molecule then binds and unzips the double helix of mutated or faulty DNA. Lastly, donor DNA binds with the mutated DNA and automates a mechanism to correct the DNA error. The main significance of this study is that it was done in a foetus, thus researchers had to use a method analogous to amniocentesis wherein they inserted the PNA complex into the amniotic sac (amniotic fluid) of pregnant mice whose foetuses were carrying the gene mutazione che causa la beta talassemia. Dopo un'iniezione di PNA, il 6% delle mutazioni è stato corretto. Questi topi hanno mostrato un miglioramento dei sintomi della malattia, cioè i livelli di emoglobina erano nell'intervallo normale che potrebbe essere interpretato come i topi "guariti" dalla condizione. Hanno anche mostrato un aumento del tasso di sopravvivenza. Questa iniezione era in un intervallo molto limitato, ma i ricercatori sperano che si possano ottenere tassi di successo ancora più elevati se le iniezioni sono state eseguite più volte.
Lo studio è rilevante perché non sono stati rilevati fuori bersaglio ed è stato corretto solo il DNA desiderato. Le tecniche di editing genetico come CRISPR/Cas9, sebbene siano più facili da usare per scopi di ricerca, è ancora controverso perché taglia il DNA ed esegue errori fuori sede poiché danneggiano anche un normale DNA fuori bersaglio. A causa di questa limitazione non sono ideali per la progettazione di terapie. Considerando questo fattore, il metodo mostrato nell'attuale studio si lega solo al DNA bersaglio e lo ripara e non mostra errori fuori sede. Questa qualità mirata lo rende ideale per le terapie. Un tale metodo nel suo design attuale potrebbe anche essere potenzialmente utilizzato per "curare" altre condizioni in futuro.
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Fonte (s)
Ricciardi AS et al. 2018. Consegna in utero di nanoparticelle per l'editing del genoma site-specific. Nature Communications. https://doi.org/10.1038/s41467-018-04894-2
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