BY Isabella Munford
2018 proved to be an exciting year in more ways than one. There was a Royal wedding, a world cup, a ‘Brexit’ to discuss and yet amongst all this, numerous important scientific discoveries were made. These are three important findings in the field of life sciences from 2018 that you should know about:
Tumour suffocating nanorobots:
In 2018, science fiction became reality with a discovery that captured the imagination of the media and scientists globally when published in Nature Biotechnology in February. Underneath the headline lies an interesting piece of nanotechnology with the potential to increase the precision of drug delivery in cancer.
“In 2018, science fiction became reality with a discovery that captured the imagination of the media and scientists globally”
Scientists developed a DNA origami molecule with a DNA aptamer on the outside and thrombin on the inside. An aptamer is a peptide or oligonucleotide that is capable of binding specific target molecules. In this case, the target molecule is nucleolin, a protein specifically expressed on tumour-associated endothelial cells. The aptamer not only acts as a targeting domain, but when it binds to nucleolin, the DNA origami molecule also mechanically opens to release the thrombin. Thrombin then activates coagulation at the tumour site to induce intravascular thrombosis to eventually cause tumour necrosis, or death, and the inhibition of tumour growth.
This mechanism is widely applicable to most tumour types, occurs rapidly (within a few hours) and carries a reduced risk of resistance development. Furthermore, this form of nanotechnology not only affected the primary tumour, but also prevented metastasis, indicating therapeutic potential. Although promising, this study only looked at melanoma mouse models and has not yet been tested in humans.
The field of cloning has substantially evolved since Dolly the sheep, and nothing proves this more than a recent ground-breaking study published in Cell in February 2018, in which macaque monkeys were cloned. A group of scientists at the Institute of Neuroscience at the China Academy of Sciences in Shanghai successfully cloned a pair of macaque monkeys using somatic cell nuclear transfer, a similar technique to that used to clone Dolly.
The method applied in this study involved slightly modifying the standard technique used for cloning whereby DNA of a donor cell is injected into an enucleated oocyte. An enucleated oocyte is an ovarian cell without a nucleus. One of the changes made in this study was to undo the chemical modification that occurs in the DNA when embryonic cells develop into specialised cells. Using foetal cells, the researchers created over 100 cloned embryos of which around 70 were implanted into surrogate monkeys. Two macaque monkeys successfully survived gestation and are reported to be healthy by the researchers.
“Two macaque monkeys successfully survived gestation and are reported to be healthy by the researchers.”
More recently, on the 24th of January this year, the official Xinhua news agency announced that researchers at the same Institute of Neuroscience had successfully cloned five gene-edited macaque monkeys. All the monkeys carry a mutation of BMAL1 that had been altered in the donor using gene-editing technology. This mutation creates monkey models that allow the research of circadian rhythm disorders.
Although cloned animals provide certain advantages when it comes to studying human diseases as they eliminate genetic confounding factors, this type of technology still raises several concerns. Some people are worried that this technique may be utilised in private clinics in China, as there are no strict laws that regulate reproductive cloning.
Mice with two mothers and no fathers:
In November 2018, a study was published in Cell Stem Cell indicating that scientists had developed a new technique to allow for same-sex reproduction in mammals. This had never been achieved before using bipaternal reproduction (two fathers) and bimaternal reproduction (two mothers) had only produced mice with defective growth.
Using gene-editing, the scientists were able to delete three imprinting regions of the genome from parthenogenetic haploid embryonic stem cells (ESCs) containing maternal DNA and inject them into metaphase II (MII) oocytes from another female mouse. Imprinting regions are regions of DNA that are expressed in a parent-of-origin-specific manner and undergo various epigenetic changes such as histone methylation. The scientists found that the deletion of these three imprinting regions restored normal growth of the female bimaternal mice, and they actually proceeded to have children of their own.
Producing offspring from two fathers was trickier: seven imprinted regions were deleted in androgenetic haploid ESCs before they were injected into an enucleated oocyte along with sperm. This resulted in embryos containing only genomic DNA from two males and resulted in the birth of live bipaternal mice, however, they only survived for two days.
Experts have claimed that this method is not applicable to humans due to the “extensive genetic manipulation” that leads to a high risk of severe abnormalities. They have acknowledged that whilst this is a step in that direction it will take more research in different animal models until this technique can be used safely in humans.
Last year proved to be an exciting and significant year for life science research and certainly suggests that as research moves forward there will only be more impressive discoveries in the year to come.