Ang pag-aaral ay nagpapakita ng pangako para sa paggamot sa genetic na sakit sa isang mammal sa panahon ng pagbuo ng pangsanggol sa unang tatlong buwan ng pagbubuntis
A genetiko Ang disorder ay isang kondisyon o sakit na sanhi ng abnormal na pagbabago o mutasyon sa DNA ng isang tao sa gene. Ang aming 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 genetiko 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 genetiko 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 genetiko 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.
Paggamot genetiko condition in an unborn baby
For the first time the revolutionary gene editing technique has been used to cure a ‘genetiko 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 genetiko mutation if corrected would reduce the impact of the mutation on embryo-to-foetal development. There are chances that a severe genetiko condition could even be cured and the baby is born without the unintended birth defects.
Sa pag-aaral na ito na inilathala sa Nature Communications researchers have used a peptide nucleic acid-based gene editing technique. This technique has been used before to treat beta thalassemia – a genetiko 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 genetiko 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 mutation na nagdudulot ng beta thalassemia. Pagkatapos ng isang iniksyon ng PNA, 6 na porsiyento ng mga mutasyon ang naitama. Ang mga daga na ito ay nagpakita ng pagpapabuti sa mga sintomas para sa sakit ibig sabihin, ang mga antas ng hemoglobin ay nasa normal na hanay na maaaring ipakahulugan bilang ang mga daga ay 'gumaling' sa kondisyon. Nagpakita rin sila ng pagtaas ng survival rate. Ang pag-iniksyon na ito ay nasa isang napakalimitadong saklaw ngunit ang mga mananaliksik ay umaasa na kahit na mas mataas na mga rate ng tagumpay ay maaaring makamit kung ang mga iniksyon ay ginawa ng maraming beses.
Ang pag-aaral ay may kaugnayan dahil walang mga off-target na nabanggit at tanging ang nais na DNA lamang ang naitama. Ang mga diskarte sa pag-edit ng gene tulad ng CRISPR/Cas9 bagama't mas madaling gamitin para sa mga layunin ng pananaliksik, ito ay kontrobersyal pa rin dahil pinuputol nito ang DNA at nagsasagawa ng mga error sa labas ng site habang sinisira din ng mga ito ang isang off-target na normal na DNA. Dahil sa limitasyong ito, hindi sila angkop para sa pagdidisenyo ng mga therapy. Isinasaalang-alang ang salik na ito, ang paraan na ipinakita sa kasalukuyang pag-aaral ay nagbubuklod lamang sa target na DNA at nag-aayos nito at nagpapakita ng nil offsite na mga error. Ang naka-target na kalidad na ito ay ginagawang perpekto para sa mga panterapeutika. Ang ganitong paraan sa kasalukuyang disenyo nito ay maaari ding magamit upang 'gamutin' ang ibang mga kondisyon sa hinaharap.
***
{Maaari mong basahin ang orihinal na papel ng pananaliksik sa pamamagitan ng pag-click sa link ng DOI na ibinigay sa ibaba sa listahan ng (mga) binanggit na pinagmulan}
Pinagmulan (s)
Ricciardi AS et al. 2018. In utero nanoparticle delivery para sa site-specific genome editing. Nature Communications. https://doi.org/10.1038/s41467-018-04894-2
***
