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GeneOnline’s Top Ten Headlines of the Year
By Rajaneesh K. Gopinath, Ph.D.
As 2019 comes to a close, we look back to some of the major scientific breakthroughs and headlines that lit up the year. From several interesting stories, we summarize the ones that caught our attention.
1. Scientists Create Novel Synthetic DNA
The human nucleic acids consist of four nucleotide bases, A, T (or U), C and G but for a long time, scientists have tried to increase that number. Last February, a new study funded by NASA and led by the Foundation for Applied Molecular Evolution was published in Science. Hachimoji DNA (Japanese for ‘eight letters’) refers to the creation of an additional four nucleotide bases that were demonstrated in both DNA and RNA analogs.
The new codes, P, B, Z, and S follow the same principle of purine pyrimidine base-pairing using hydrogen bonds where S pairs with B and P with Z. The additional bases are similar to one of the naturally occurring bases but have variations in their bonding patterns. According to the authors, the synthetic DNA could be used to create new proteins, devise novel nanostructures, DNA barcoding and increase the ability to store data in DNA.
2. New Drug Approved for Post-partum Depression
Postpartum depression (PPD) is a crippling obstacle faced by women after childbirth and is often characterized by anxiety, a feeling of ineptitude and a sense of doom. It is characterized by the decrease in the natural production of the allopregnanolone hormone post-pregnancy. In March, the FDA approved Sage therapeutics’ Brexanolone (Zulresso), a synthetic form of allopregnanolone, making it the first and only treatment for PPD.
The approval was based on the results yielded from three multicenter, randomized, double-blind, placebo-controlled trials, involving patients between 18 and 45 years suffering from moderate to severe PPD. In comparison to the placebo, the drug recorded a significant reduction in the Hamilton Rating Scale for Depression (HAM-D) total score, when delivered as a single infusion over 60 hours. A reduction of symptoms was also seen at 24 hours.
3. New Male Birth Control Pill Passes Safety Tests
To control the rising population and the consequent burden on our planet, hormonal contraception for men becomes a necessity. Despite the existing options of birth control, statistics tell us that about 40–45% of pregnancies across the world are unplanned. Several studies have been conducted with candidate molecules hitherto but a male hormonal contraceptive still eludes the market.
Earlier this year, a new male birth control pill, 11-beta-methyl-19-nortestosterone dodecylcarbonate passed safety tests. 11-beta-MNTDC is a modified testosterone that has the combined actions of both androgen and progesterone. A study funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, enrolled 40 healthy men receiving two doses of the pill, with 10 of them randomly receiving placebo treatment. All the study participants were reported to clear the safety tests with mild side effects. If everything goes well, a safe male contraceptive could be expected for use in around 10 years.
4. Discovery of gut bacterial enzymes that convert type A to ‘Universal’ type O blood
Blood transfusions are pivotal for a majority of clinical procedures. However, donors are scarce and the shortage of blood and platelets still exists. To overcome blood shortage and minimize the time consumed by blood typing, scientists have labored over three decades to eliminate blood group antigens. Of the three main antigen‐modulation strategies undertaken, the manipulation of the ABO system is the most preferred.
As early as the 1940s, scientists discovered that certain microbes displayed enzymatic activity that could alter the ABO blood type. This year, using functional metagenomic screening of the human gut microbiome, researchers from the University of British Columbia, identified an enzyme pair from an obligate anaerobe Flavonifractor plautii. The authors demonstrated that the newfound enzymes are 30% better in converting type A to type O blood as compared to the ones previously identified.
5. The Return of Biogen’s Aducanumab
In March, Biogen and its partner Eisai shocked the world by discontinuing clinical trials of aducanumab, an investigational human monoclonal antibody for the early treatment of Alzheimer’s disease. In a sudden turn of events in late October, they made an equally surprising U-turn by reviving plans to pursue regulatory approval. The new development positively impacted the stock value of Biogen as it almost recovered the losses suffered earlier in the year.
New analyses showed that the drug met its primary endpoint in the EMERGE study by showing “a significant reduction in clinical decline”, with improvements in cognition and function such as memory, orientation, and language. Besides, a subset of patients from the ENGAGE study who received higher exposure to the drug, support their findings from EMERGE. The company plans to file for approval in early 2020. If approved, it would become the first therapy to demonstrate that efficient removal of Aβ could lead to the reversal of clinical decline, a validation of the amyloid-beta hypothesis.
6. CRISPR and Vertex Release First Clinical Trial Data of a Gene-Editing Candidate Sponsored in the US
In November, CRISPR Therapeutics and Vertex Pharmaceuticals released encouraging, interim data of two patients, one with severe sickle cell disease and another with beta-thalassemia. They were enrolled in the ongoing, Phase 1/2 clinical trials CLIMB-SCD-121 and CLIMB-Thal-111 respectively that tested the investigational CRISPR/Cas9 gene-editing therapy CTX001.
The treatment involves collecting the patient’s hematopoietic stem and progenitor cells, editing genes with CRISPR-cas9 technology, and infusing it back into them. The results showed that both patients had normal hemoglobin levels with only mild anemia. The sickle cell patient had 11.3 g/dL of hemoglobin after receiving four months of CTX001, no longer suffering from the threat of vascular occlusion crisis and chronic pain. On the other hand, the patient with severe beta-thalassemia had a total hemoglobin of 11.9 g/dL after 9 months of CTX001. He was no longer required to receive routine blood transfusions more than once a month.
7. Pig Monkey Chimeras
A team in China created the world’s first pig-primate chimeras marking a significant landmark in lab-grown organs. The piglets that were engineered to have some amount of cynomolgus monkey (crab-eating macaque) cells that migrated to the heart, liver, lungs, spleen, and skin. Although the piglets died within a week of birth, the authors opine that this study could serve as the impetus for xenogeneic organogenesis, a process of growing human organs in animals for transplantation.
8. Approval of World’s First Ebola Vaccine
Ebola virus disease (EVD) is a rare but fatal disease transmitted from wild animals but spread through human-to-human transmission. The causative viruses of EVD are mostly found in sub-Saharan Africa and the few cases that were found in the US were the result of infected travelers or health care workers who treat patients.
Towards the end of 2019, following the European Commission, the USFDA also approved the first vaccine for the prevention of EVD caused by Zaire ebolavirus in individuals 18 years of age and older. Ervebo, developed by Merck is expected to be available for use in the third quarter of 2020. Administered as a single-dose injection, the vaccine is genetically engineered to contain an attenuated protein from Zaire ebolavirus. The approval is supported by several studies, with the one conducted in Guinea during the 2014-2016 outbreak being the central one.
“Approval of this vaccine by the FDA represents another important milestone in the global response to Ebola Virus Disease and stands as a tremendous accomplishment by a unique global partnership,” said Dr. Roger M. Perlmutter president, Merck Research Laboratories.
9. Chinese Court Punishes ‘CRISPR babies’ Researchers
CRISPR/Cas9 gene editing, the biggest breakthrough of the last decade, is expected to shape our future significantly. But like any powerful technology, there is always a danger of it getting abused. In late 2018, those fears were realized when Chinese scientist, He Jiankui announced his creation of “CRISPR babies”. This is because, although CRISPR yields precise modifications of DNA, there have been concerns of unintended off-target mutations.
The researchers claimed that the intention was to immunize the twin baby sisters Lulu and Nana against HIV by modifying the CCR5 gene in the embryo. However, a recent examination of the unpublished manuscripts by the MIT Technology Review involving four experts found that the claims made by He and his team were not supported by data.
On December 30th, the Shenzhen court in South China punished He and his coworkers Zhang Renli and Qin Jinzhou for jointly carrying out human embryo gene editing and reproductive medical activities for reproductive purposes. The court found that the trio conspired since 2016 and has deliberately violated scientific regulations and crossed ethical boundaries. While He Jiankui is sentenced to a three-year prison sentence including a fine of 3 million Chinese yuan (US$430,000), the others are given lesser sentences.
10. The Development of Prime Editing
Of the several attempts made to tackle off-target mutations of CRISPR/Cas9 gene editing, the prominent ones have been from the lab of David Liu and colleagues from the Broad Institute. While base editing is capable of modifying a single base in a gene, the prime editing technology developed this year offers greater target flexibility in achieving precision.
The primer editor complex that comprises of a modified Cas9, reverse transcriptase, and pegRNA functions as follows. The guide sequence of the pegRNA targets and binds to a specific mutated site which the Cas9 nicks. The primer sequence of the pegRNA helps it to hybridize with the 3’end of the nicked DNA. This double strand gets recognized by the reverse transcriptase which then copies the information from the prime template to the host’s genome.
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