Lifeboat Foundation

Principal investigator Eric Pierce pointed out that the trial shows that gene therapy for hereditary vision loss is a worthy pursuit for future research. He believes the early research is promising.

“It’s a big deal to hear how thrilled they were to finally be able to see food on their plates,” said Pierce. “These were individuals who couldn’t read a single line on an eye chart. They had no treatment options, which is an unfortunate reality for most people with inherited retinal disorders.”

The goal is to inject CRISPR so that it reaches the retina to restore the ability to produce genes and proteins.

Blocking enzyme SMYD5 inhibits tumour growth and primes lab models for combination therapy, offering hope for more effective treatments.

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” »

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.

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.

A research team from the University of Basel has succeeded in synthesizing simple, environmentally sensitive cells complete with artificial organelles. For the first time, the researchers have also been able to emulate natural cell-cell communication using these protocells—based on the model of photoreceptors in the eye. This opens up new possibilities for basic research and applications in medicine.

For example, enhancers (DNA segments that promote gene expression) and gene promoters (regions that initiate transcription) can interact more readily in open, accessible regions of chromatin.

On the other hand, DNA in tightly packed chromatin regions remains less active. Through analyzing these contact points, researchers have developed models to map chromatin configurations across various species, such as humans, mice, birds, and more recently, turtles.

In a recent paper published in the journal Genome Research, Valenzuela’s team described the chromatin arrangement in the genomes of two turtle species, the spiny softshell and northern giant musk turtles, uncovering a structure previously unobserved in other organisms.