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Genetically modified baby boy - with 3 parents

New, cheap and accurate DNA-editing techniques called CRISPR-Cas9 and SNT, or single nucleic targeting, are allowing for gene modification in humans. It is not science fiction anymore. In a first, a baby boy with modified DNA has been born in Mexico to overcome a mitochondrial disease that claimed the life of his two earlier sibblings.


On September of 2015, The Francis Crick Institute in London announced they would apply to edit human DNA in embryos, this was followed by the August 4, 2016 announcement by the National Institutes of Health Office of Science Policy that United States scientists may now edit DNA in human embryos and adults, using the CRISPR technique.

However, the first US citizen — a baby boy — was born with modified mtDNA in Mexico, just five months ago. The infant is now pleasing his parents, grandparents, doctors and nurses, using both parents' DNA and a third adult's mitochondria, to begin life without the mitochondrial disease that killed his prior two siblings, Leigh syndrome. Leigh's is a severe neurological disorder that usually appears in the first year of life, is characterized by a progressive loss of mental and movement ability, resulting in death before age 3 due to respiratory failure.

Appearing in the magazine Society for Reproductive Endocrinology and Infertility, which broke the story, a smiling Dr. John Zhang, fertility specialist at New Hope Fertility Center, New York City, presents the newborn he helped into the world.


The single nucleic targeting or SNT procedure was conducted in Mexico where human embryo manipulation is not as restricted as in the USA.


mtDNA, or mitochondria DNA, converts food energy (calories) into a form that cells use to divide, grow into tissues and form organs — its loss or failure deprives cells energy for continued development. Mitochondrial DNA is passed from mothers to sons and daughters only through the female egg, so sons cannot pass mtDNA mutations along to their children. If mom carries a mtDNA mutation, her newborn faces a number of life-threatening conditions.

Zhang used an tchnique called spindle nuclear transfer, SNT, to create five human embryos. He removed the nucleus from each of the eggs collected from the mother — the bulk of all human DNA is in the cell nucleus. Each of mom's nuclei were then inserted into a donor egg stripped of its original nucleus, but containing healthy mitochondria without mutations — from a donor.


Through SNT, each egg now has mitochondrial DNA from the healthy donor and all of its' nuclear DNA is from the mother. Five donors eggs were prepared, then fertilized with the husband’s sperm. Now each embryo has mother and father's combined DNA as in any normal fertilized egg — but, donor mitochondria to energize fetal, and later baby's growth.


Only one of the embryos created for this couple had a normal number of chromosomes result after fertilzation. That one was transferred into mom.

In addition to New Scientist, the only other information on this event is an abstract to appear in an upcoming issue of Fertility and Sterility of a talk to be presented at the American Society for Reproductive Medicine meeting in October 2016. The abstract says the baby is “doing well” at 3 months, and that roughly 1 to 2% of the mother’s diseased mitochondrial DNA persist in his tested cells — but, the baby does not appear to have Leigh syndrome. Zhang declined interviews to protect the family's privacy.

Norbert Gleicher, fertility specialist at the Center for Human Reproduction in New York City, believes the New York team’s decision to work in Mexico is due to all the obstacles in trying such an experimental procedure — or even applying for approval to offer it — in the United States. Gleicher has wanted a meeting with the U.S. Food and Drug Administration (FDA) to discuss mitochondrial DNA replacement for U.S. patients, as a treatment for infertility. “We have not even been able to get an appointment,” he adds.


Swedes edit human embryo DNA Sep. 22, 2016

Swedish scientist Fredrik Lanner has started to edit healthy human embryos, NPR reports. Lanner uses the gene editing technology CRISPR-Cas9 to find new treatments for infertility and miscarriage.

He will deactivate genes in embryos to see what roles they play in early development. U.K. scientists were given the go-ahead for similar research earlier this year. Although some worry gene editing will lead to designer babies or even new hereditary diseases, Lanner says basic research like his is necessary to know how to avoid such situations.


The regulatory situation in the United States “kind of doesn’t make any sense,” Gleicher argues:“because what it results in is exactly what you have been witnessing”—essentially, an experiment that moves “to places with no supervision.”

Dieter Egli PhD, stem cell biologist at Columbia University, agrees. “For me, the lesson here is that it’s very important that regulatory agencies like the FDA move forward,” he said. “This could have been done in the United States by groups that have many years and decades of research [experience].”

Clinical embryologist Jacques Cohen of Reprogenetics in Livingston, New Jersey, who has previously advised Zhang’s team about regulatory issues, defends the decision :“Just because this was done in Mexico doesn’t mean it was not done ethically,” says Cohen, who himself led controversial fertility experiments in the 1990s involving the transfer of cytoplasm, in which the resulting babies also had three genetic parents.

Zhang is not new to embryo modification. In China in 2003, he swapped a nucleus from one egg to another, though the egg was already fertilized. Reported in The New York Times, the research appeared only last month, in Reproductive BioMedicine Online. The 30-year-old woman who became pregnant, lost her twins before birth.

In 2009, Shoukhrat Mitalipov PhD, of the Oregon Health & Science University in Portland achieved similar success in macaque monkeys. Like others, Mitalipov said in a statement to Science that it was troubling that “desperate parents” were being forced to “countries with less oversight.” He attributes the failure to congress for blocking the FDA from allowing mitochondrial replacement to be attempted.


The United Kingdom, as well as a U.S. National Academy of Sciences, has given approval to mitochondrial transfer to prevent disease. In the United States, however, Congress has blocked FDA from allowing any experimental procedures.


Abstract "Pregnancy derived from human zygote pronuclear transfer in a patient who had arrested embryos after IVF"
Nuclear transfer of an oocyte into the cytoplasm of another enucleated oocyte has shown that embryogenesis and implantation are influenced by cytoplasmic factors. We report a case of a 30-year-old nulligravida woman who had two failed IVF cycles characterized by all her embryos arresting at the two-cell stage and ultimately had pronuclear transfer using donor oocytes. After her third IVF cycle, eight out of 12 patient oocytes and 12 out of 15 donor oocytes were fertilized. The patient's pronuclei were transferred subzonally into an enucleated donor cytoplasm resulting in seven reconstructed zygotes. Five viable reconstructed embryos were transferred into the patient's uterus resulting in a triplet pregnancy with fetal heartbeats, normal karyotypes and nuclear genetic fingerprinting matching the mother's genetic fingerprinting. Fetal mitochondrial DNA profiles were identical to those from donor cytoplasm with no detection of patient's mitochondrial DNA. This report suggests that a potentially viable pregnancy with normal karyotype can be achieved through pronuclear transfer. Ongoing work to establish the efficacy and safety of pronuclear transfer will result in its use as an aid for human reproduction.

Related articles
Improved Identification of Mitochondrial Genes as Passed from Mother to Child
A study which highlights shortcomings of current genetic testing methods to prevent certain genetic disorders.

Mitochondrial genes and disease inheritance Mitochondrial diseases are maternally inherited gene disorders that cause many debilitating conditions without any cures. Now, Salk Institute reports a successful gene-editing technology to prevent passing mutated mitochondrial DNA from mothers to offspring in mice.


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Oct 3, 2016   Fetal Timeline   Maternal Timeline   News   News Archive   



John Zhang MD, of New Hope Fertility Center in New York City, holding newborn boy
whose faced is blurred for his and his family's privacy.
Image Credit: Public Domain


 


Phospholid by Wikipedia

 

Phospholid by Wikipedia