It is argued that formation of a tumour-intrinsic niche is a prerequisite for BRAF-mutant CRC seeding to distant organs and that interference with niche formation may help avoid metastatic relapse.
It is concluded that bridging the gap between foundational CRISPR research and its real-world applications is imperative and future efforts should focus on democratizing tools via open-source platforms, advancing delivery systems, and fostering sustainable innovation through synthetic biology integration to fully realize the transformative potential of genome editing in organisms beyond model organisms.
Variants of uncertain significance (VUS) in the LMNA gene represent a major challenge in clinical genetics, as insufficient functional evidence limits their interpretation and clinical decision-making in laminopathies, including dilated cardiomyopathy (DCM). Here, we generated two isogenic induced pluripotent stem cell (iPSC) lines carrying homozygous LMNA variants, c.293A > G (p.Glu98Gly) and c.439G > A (p.Ala147Thr) by prime editing of a healthy donor iPSC line. Both variants are located within Coil 1B domain of lamin A. The edited iPSC lines retain normal morphology, pluripotency, genomic integrity, and trilineage differentiation capacity, providing a valuable platform for functional characterization and potential clinical reclassification of LMNA VUS.
A virus-like particle (VLP)-based toolkit that delivers diverse CRISPR editing modalities to human monocytes, macrophages and dendritic cells with high efficiency while preserving viability and innate immune responsiveness is presented.
Findings provide direct functional evidence that szl regulates median caudal patterning in goldfish and suggest that szl-dependent modulation of the Chordin/BMP network can generate twin-tail-like caudal morphology.
The landmark derivation of induced pluripotent stem cells (iPSCs) sparked an enormous range of research on development of diverse cell populations. Perhaps no aspect of this work has been as productive as studies on blood and immune cell production. Indeed, essentially all human blood cell populations can be derived from human iPSCs. While derivation of transplantable hematopoietic stem cells (HSCs) from iPSCs has been relatively challenging, clinical translation of iPSC-derived immune cells has been particularly productive. Notably, more patients have been treated with iPSC-derived natural killer (NK) cells than any other iPSC-derived cell type. Use of iPSCs provides a key platform to incorporate multiplexed gene edits before differentiation, enabling NK cells to be engineered with tumor-targeting CARs, cytokine support for improved persistence, enhanced tumor trafficking, and resistance to host immune rejection, modifications uniformly expressed across the entire cellular product. While T cells, macrophages and other immune cells can be produced from human iPSCs, iPSC-derived NK cells have been the most widely used in clinical trials for treatment of refractory malignancies, as well as autoimmune disease. This review summarizes research with a focus on clinical translation of iPSC-derived immune cells, as well as highlights continued challenges and prospects of this field.
Generative AI
A new method for surgically removing training examples from a model reveals that as datasets grow, the link between what a model learns and what it produces dissolves.
In his latest book, Professor Eugene Fitzgerald examines the forces that turn breakthroughs into value — and why innovation resists simple formulas.
General Science
