Later Summer 2015 Genetics Updates
The Right way to use Genetic Modification
Throughout history, people have relied on plants for medicines. Even modern drugmakers get about half their new drugs from plants. But that’s harder to do when plants are slow growing and endangered, as is the Himalayan mayapple (Podophyllum hexandrum). The short, leafy plant was the original source of podophyllotoxin, a cytotoxic compound that’s the starting point for an anticancer drug called Etoposide. The drug has been on the U.S. market since 1983 and is used to treat dozens of different cancers, from lymphoma to lung cancer. Today, podophyllotoxin is mainly harvested from the more common American mayapple. But this plant is also slow growing, producing only small quantities of the compound.
Mayapples churn out podophyllotoxin to defend against would-be munchers. To do so, the plants use a step-by-step approach to synthesize their chemical defense. But because the synthetic pathway of the compound had never been worked out, no one knew precisely which genes were involved in stitching together the molecule. What researchers did know was that podophyllotoxin isn’t always present in the plant. “It’s only when the leaf is wounded that the molecule is made,” says Elizabeth Sattely, a chemical engineer at Stanford University in Palo Alto, California, who led the current research effort.
Sattely and her graduate student Warren Lau reasoned that the podophyllotoxin-building proteins were likely themselves only made by the plant in response to an injury. So the pair made tiny punctures in the leaves of healthy Himalayan mayapples provided to them by a commercial nursery, testing them before and after to see which new proteins appeared around the damaged tissue. They discovered 31, which they categorized by probable function.
The pair then narrowed the likely candidates for enzymes in podophyllotoxin production by focusing on members of four classes known to carry out the right types of chemical reactions. They then spliced genes for each of these enzymes into bacteria known to infect Nicotiana benthamiana, a fast-growing relative of tobacco that serves as a sort of lab rat of plant biologists. The bacteria readily infect tobacco and insert their genes into the plant tissue. Sattely and Lau inserted numerous combinations of genes for the enzymes they thought might produce their desired compound. As they report online today in Science, they eventually hit on a group of 10 enzymes that allowed the plant to make a molecule called (-)-4’–desmethyl-epipodophyllotoxin, a direct precursor to Etoposide and a potent cancer drug in its own right.
https://archive.is/69Hgu
Gene modification in untransformed human intestinal cells is an attractive approach for studying gene function in intestinal diseases. However, because of the lack of practical tools, such studies have largely depended upon surrogates, such as gene-engineered mice or immortalized human cell lines. By taking advantage of the recently developed intestinal organoid culture method, we developed a methodology for modulating genes of interest in untransformed human colonic organoids via electroporation of gene vectors. Here we describe a detailed protocol for the generation of intestinal organoids by culture with essential growth factors in a basement membrane matrix. We also describe how to stably integrate genes via the piggyBac transposon, as well as precise genome editing using the CRISPR-Cas9 system. Beginning with crypt isolation from a human colon sample, genetically modified organoids can be obtained in 3 weeks
https://archive.is/tE2DL
The Hinxton Group, which describes itself as an international consortium on stem cells and bioethics, also said in a statement released on Wednesday that the engineering of GM babies—a concept commonly called designer babies—could be "morally acceptable" in the future, although it said it was not in favour of the procedure at present.
Currently, the U.S. National Institutes of Health (NIH) refuses to provide funding for any research involving the genetic modification of human embryos, The Guardian reports. In the U.K., the use of embryos which have been genetically altered where these edits could be passed on to offspring is illegal.
They claimed that new gene-editing technology, which could be used to correct genetic defects or introduce beneficial changes, "provides vast scope for applications in human disease and health" and that genome editing has "tremendous value" for scientific research.
Modern gene-editing tools such as CRISPR/Cas9—a technique which can reportedly edit the genomic sequence in a highly targeted way—are "not only very precise, but also easy, inexpensive, and, critically, very efficient," the group said.
Earlier this year, Chinese scientists reportedly edited the genomes of human embryos in what was described as "a world first" by the journal Nature.
https://archive.is/sCnC4