First use of precision editing to alter a single gene to study human embryo development reveals role of master gene

Amazing stuff!

Notice we are now going way beyond the famous CRISPR/Cas9 gene editing!

In my opinion, the first gene to be removed from humans is the sneezing gene!

"Research ... has shown that a genome editing technique can be used to alter a single gene in human embryonic cells, enabling the study of very early human development in unparalleled detail.

The technique, called base editing, is a more precise version of the genome editing technique CRISPR/Cas9. It can change a single nucleotide base pair - the basic building block of DNA - within a human genome of approximately 3 billion base pairs. 

Using base editing, the researchers blocked a gene called NANOG in very early-stage human embryos, and found that the cells of the early embryo could not develop into more specialised pluripotent cells called the epiblast - which later form the body. ..."

From the abstract:

"Understanding how the first cell lineages in human development are specified and maintained has fundamental importance and clinical implications for regenerative medicine, infertility and pregnancy loss.

While mouse models have provided valuable insights into transcription factors regulating early development, translating these findings to human embryos has been limited by ethical, technical and biological constraints.

Functional studies of transcription factors in human embryos have been hindered by nuclease-based genome-editing approaches that induce genotoxicity. 

To overcome this, we applied adenine base editing (ABE8e) to precisely target an exon splice donor site, resulting in a splicing defect and functional knockout of NANOG, representing the first application of base editing to study a developmental regulator in human embryos.

This approach did not trigger genotoxicity and showed limited off-target editing.

Loss of NANOG disrupts pluripotent epiblast specification and instead cells differentiate toward a primitive endoderm (yolk sac) or trophectoderm (placental) transcriptional programme. Retention of primitive endoderm differentiation in NANOG-edited human embryos reveals a functional compensation distinct from mouse, underscoring the importance of directly investigating human development. Our findings demonstrate an essential role for NANOG in human pluripotency and epiblast specification, and highlight the utility of base editing for functional interrogation of human development."

First use of precision editing to study human embryo development reveals role of master gene | University of Cambridge "Scientists have, for the first time, used an extremely precise genome editing technique called base editing to study gene function in human embryos. They found that a gene called NANOG is essential for forming the future body from an embryo."

Base editing reveals an essential role for NANOG in human embryogenesis (no public access)

Day 6 human embryos showing the effect of NANOG presence versus absence. Normal embryo (left)