Microbial systems have been synthetically engineered to deploy therapeutic payloads in vivo.

To enable effective cancer vaccination, we developed an engineered bacterial system in probiotic Escherichia coli Nissle 1917 (EcN) to enhance expression, delivery and immune-targeting of arrays of tumour exonic mutation-derived epitopes highly expressed by tumour cells and predicted to bind major histocompatibility complex (MHC) class I and II (Fig. 1a). This system incorporates several key design elements that enhance therapeutic use: optimization of synthetic neoantigen construct form with removal of cryptic plasmids and deletion of Lon and OmpT proteases to increase neoantigen accumulation, increased susceptibility to phagocytosis for enhanced uptake by antigen-presenting cells (APCs) and presentation of MHC class II-restricted antigens, expression of listeriolysin O (LLO) to induce cytosolic entry for presentation of recombinant encoded neoantigens by MHC class I molecules and T helper 1 cell (T_H1)-type immunity and improved safety for systemic administration due to reduced survival in the blood and biofilm formation.

To assemble a repertoire of neoantigens, we conducted exome and transcriptome sequencing of subcutaneous CT26 tumours. Neoantigens were predicted from highly expressed tumour-specific mutations using established methods^14,15, with selection criteria inclusive of putative neoantigens across a spectrum of MHC affinity^16,17. Given the importance of both MHC class I and MHC class II binding epitopes in antitumour immunity^15,18,19, we integrated a measure of wild-type-to-mutant MHC affinity ratio—termed agretopicity^17,20—for both epitope types derived from a given mutation, to help estimate the ability of adaptive immunity to recognize a neoantigen. Predicted neoantigens were selected from the set of tumour-specific mutations satisfying all criteria, notably encompassing numerous recovered, previously validated CT26 neoantigens¹⁵ (Extended Data Fig. 1a).

We then sought to create a microbial system that could accommodate the production and delivery of diverse sets of neoantigens to lymphoid tissue and the tumour microenvironment (TME). For the purpose of assessing neoantigen production capacity, a prototype gene encoding a synthetic neoantigen construct (NeoAg^p) was created by concatenating long peptides encompassing linked CD4⁺ and CD8⁺ T cell mutant epitopes—previously shown as an optimal form for stimulating cellular immunity²¹—derived from CT26 neoantigens (Extended Data Fig. 1b and Extended Data Table 1). The construct was cloned into a stabilized plasmid²² under constitutive expression and transformed into EcN; however, both immunoblot and enzyme-linked immunosorbent assay (ELISA) assessment showed low production of the prototype construct by EcN across several tested promoters (Extended Data Fig. 1c).

Scientists from Vilnius University’s (VU) Life Sciences Center (LSC) have discovered a unique way for cells to silence specific genes without cutting DNA. This research, led by Prof. Patrick Pausch and published in the journal Nature Communications, reveals a new way to silence genes that is akin to pressing a “pause” button on certain genetic instructions within cells.

A trio of research papers from Stanford Medicine researchers and their international collaborators transforms scientists’ understanding of how small DNA circles — until recently dismissed as inconsequential — are major drivers of many types of human cancers.

The papers, published simultaneously in Nature on Nov. 6, detail the prevalence and prognostic impact of the circles, called ecDNA for extrachromosomal DNA, in nearly 15,000 human cancers; highlight a novel mode of inheritance that overthrows a fundamental law of genetics; and describe an anti-cancer therapy targeting the circles that is already in clinical trials.

The team, jointly known as eDyNAmiC, are a group of international experts led by professor of pathology Paul Mischel, MD. In 2022, Mischel and the eDyNAmiC team were awarded a $25 million grant from the Cancer Grand Challenges initiative to learn more about the circles. Cancer Grand Challenges, a research initiative co-founded by Cancer Research UK and the National Cancer Institute in the United States, supports a global community of interdisciplinary, world-class research teams to take on cancer’s toughest challenges.

Antonia, a cloned black-footed ferret at the Smithsonian’s National Zoo and Conservation Biology Institute, has produced two healthy offspring that will help build genetic diversity in their recovering population.

The world is full of unusual unicellular organisms and microbes, many of which have not been discovered yet. In 2017, scientists identified a single-celled marine organism called Chromosphaera perkinsii in sediments collected from Hawaii. This species is estimated to be over a billion years old, making it older than the world’s most ancient animals. Researchers determined that this species has significant similarities to some animal embryos, though it is typically unicellular. The findings, which have been reported in Nature, suggested that some of the genetic mechanisms underlying complex life are present in C. perkinsii, or that it has evolved those characteristics independently.

The investigators noted that this study seems to answer the question of whether the chicken came before the egg; it was apparently the egg, since the genetic tools for making eggs existed prior to the emergence of chickens.