“Polygenic Adaptation”
Researchers at Northwestern have discovered a genetic "kill code" that might enable the destruction of cancer cells.
This novel new therapy "downstream" of chemo might destroy cancer cells without affecting the body's immune system.
While no animal trials have been conducted, this potential therapy could signal the demise of chemotherapy.
Abstract—Many small-interfering (si)RNAs are toxic to cancer cells through a 6mer seed sequence (positions 2–7 of the guide strand). Here we performed an siRNA screen with all 4096 6mer seeds revealing a preference for guanine in positions 1 and 2 and a high overall G or C content in the seed of the most toxic siRNAs for four tested human and mouse cell lines. Toxicity of these siRNAs stems from targeting survival genes with C-rich 3′UTRs. The master tumor suppressor miRNA miR-34a-5p is toxic through such a G-rich 6mer seed and is upregulated in cells subjected to genotoxic stress. An analysis of all mature miRNAs suggests that during evolution most miRNAs evolved to avoid guanine at the 5′ end of the 6mer seed sequence of the guide strand. In contrast, for certain tumor-suppressive miRNAs the guide strand contains a G-rich toxic 6mer seed, presumably to eliminate cancer cells.
Mistakes in DNA are known to drive cancer growth. But a new study, from Washington University School of Medicine in St. Louis, heavily implicates a genetic phenomenon commonly known as “jumping genes” in the growth of tumors.
The study is published March 29 in the journal Nature Genetics.
Since jumping genes aren’t mutations — mistakes in the letters of the DNA sequence — they can’t be identified by traditional cancer genome sequencing. As such, this study opens up new lines of research for future cancer therapies that might target such genes.
Jumping genes, which scientists call transposable elements, are short sections of the DNA sequence that have been incorporated randomly into the genome over the long course of human evolution. The evolutionary histories of jumping genes are the subject of much current research, but viral infection is thought to play an important role in their origins.
Researchers led by Ting Wang, PhD, the Sanford C. and Karen P. Loewentheil Distinguished Professor of Medicine, have plumbed genomic databases, looking specifically for tumors whose jumping genes are driving cancer growth.
biorxiv (Research Article)
Abstract—Papillomaviruses (PVs) are ancient viruses infecting vertebrates, from fish to mammals. Although the genomes of PVs are small and show conserved synteny, PVs display large genotypic diversity and ample variation in the phenotypic presentation of the infection. Most PVs genomes contain two small early genes E6 and E7. In a bunch of closely related human PVs, the E6 and E7 proteins provide the viruses with oncogenic potential. The recent discoveries of PVs without E6 and E7 in different fish species place a new root on the PV tree, and suggest that the ancestral PV consisted of the minimal PV backbone E1-E2-L2-L1. Bayesian phylogenetic analyses date the most recent common ancestor of the PV backbone to 424 million years ago (Ma). Common ancestry tests on extant E6 and E7 genes indicate that they share respectively a common ancestor dating back to at least 184 Ma. In AlphaPVs infecting primates, the appearance of the E5 oncogene 53-58 Ma concurred with i) a significant increase in substitution rate, ii) a basal radiation, and iii) key gain of functions in E6 and E7. This series of events was instrumental to build the extant phenotype of oncogenic human PVs. Our results assemble the current knowledge on PV diversity and present an ancient evolutionary timeline punctuated by evolutionary innovations in the history of this successful viral family.
Deep in the cells of the human immune system, DNA is constantly being replicated, transcribed and even mutated — but rarely does it change dramatically. Like every other living organism, humans and their genes developed from millions of years of evolutionary pruning.
But to Yale microbiologists, altering the entire genomes of T-cells — the body’s main offensive weapon against diseases such as cancer — is as simple as putting together a Lego set.
In a new study published in the journal Nature Methods on Feb. 25, researchers at the Sidi Chen Lab at Yale have come up with a new way to use the gene-editing technology CRISPR that significantly improves the technology’s efficiency. By allowing scientists to select multiple genes to include in the same CRISPR system, scientists will now be able to edit their samples’ genomes in one go, saving time and money in the process. These findings have considerable promise for engineering T-cells that can fight off cancers such as leukemia and lymphoma.
