Lifeboat Foundation

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).

Continue reading “Probiotic neoantigen delivery vectors for precision cancer immunotherapy” »

Researchers developed MassiveFold, an enhanced AlphaFold version optimized for parallel processing, which accelerates protein structure predictions from months to hours while increasing structural diversity.

Oxford Nanopore Technologies observes that direct analysis has already enhanced research across species, disease states, and applications.

The researchers used electrospinning to produce the patch—a method where high voltage is applied to a polymer solution to produce synthetic nanofibers. The fibers are then used to make a fiber mat that may be attached to the skin like a plaster.

The researchers are still working on the patch. More research, product development and clinical trials are needed before the method is ready for use.

According to Andrea Heinz, though, it has great potential that extends beyond psoriasis treatment, “A patch containing active ingredients may be an alternative to creams and ointments in the treatment of other inflammatory skin diseases, for instance atopic eczema. It may also be useful in connection with wound healing.”

Bioluminescence is the natural chemical process of light creation in some living creatures that makes fireflies flicker and some jellyfish glow. Scientists have long been interested in borrowing the secrets of these animals’ light-producing genes to create similar effects in vertebrates, for a variety of biomedical applications.

Cern physicists searching for the telltale signs of new physics within the Large Hardon Collider have released their first results.

Author(s): Jesus Rodriguez Originally published on Towards AI. Created Using IdeogramI recently started an AI-focused educational newsletter, that already has over 170,000 subscribers. TheSequence is a no-BS (meaning no hype, no news, etc) ML-oriented newsletter that takes 5 minutes to read. The goal is to keep you up to date with machine learning projects, research papers, and concepts. Please give it a try by subscribing below:

DNA repair and DNA damage signaling pathways are critical for the maintenance of genomic stability.

In this review, Hopkins et al. review the major classes of DNA repair and damage signaling defects in cancer, the genomic instability that they give rise to, and therapeutic strategies to exploit the resulting vulnerabilities. They also discuss the impacts of DNA repair defects on both targeted therapy and immunotherapy, and highlight emerging principles for targeting DNA repair defects in cancer therapy.

This lifeform can cheat time. Could it also help us push the boundaries of biology?