Dual-target CAR-T ‘very promising’ for advanced multiple myeloma
GC012F (Gracell Biotechnologies) is an autologous, genetically engineered, bispecific CAR-T that targets B cell maturation antigen (BCMA) and CD19 proteins on the surface of cancer cells. BCMA is universally expressed on malignant plasma cells and is a well-established target for multiple myeloma, while CD19 is expressed on both myeloma cells and their progenitor cells. The […]
Blood-brain barrier–penetrating single CRISPR-Cas9 nanocapsules for effective and safe glioblastoma gene therapy
Many drugs cannot cross the blood-brain barrier (BBB), which also applies to most CRISPR-carrying vehicles. So Bingyang Shi made chemically functional nanocapsules to penetrate the BBB, according to a study recently published in Science Advances. He essentially packaged unique CRISPR-Cas9/sgRNA complexes in a coating consisting of a thin polymeric shell made of positively charged guanidine […]
Dual-target CAR-T ‘very promising’ for advanced multiple myeloma
GC012F is an autologous, genetically engineered, bispecific CAR-T that targets B-cell maturation antigen and CD19 proteins on the surface of cancer cells. The new cell therapy, which has previously received FDA orphan drug designation, is manufactured within 24 hours of apheresis using Gracell’s proprietary FasT CAR platform. A single dose of an investigational chimeric antigen […]
Targeted A-to-G base editing in human mitochondrial DNA with programmable deaminases – Cell
Jin-Soo Kim’s team has discovered how to edit the mitochondrial genome to cure mitochondrial diseases. The first step was to adapt the basic editing system to induce C-to-T substitutions in mtDNA in mice because gene editing systems, such as CRISPR-Cas9, cannot edit mtDNA. Now the Kim lab has taken the next step: inducing A-to-G substitutions […]
Potentiating adoptive cell therapy using synthetic IL-9 receptors
Researchers have shown that a synthetic IL-9 receptor allows anti-cancer T cells to do their job without the need for chemo or radiation. T cells modified with the synthetic IL-9 receptor were potent against tumours in mice, as published in Nature. This group of researchers were interested in testing modified versions of the synthetic receptor […]
CRISPR/Cas9 gRNA activity depends on free energy changes and on the target PAM context | Nature Communications
A major drawback of CRISPR-Cas9-mediated genome editing is that not all guide RNAs (gRNAs) efficiently cleave target DNA. Although the heterogeneity of gRNA activity is well recognized, the exact way in which CRISPR-Cas9 activity is regulated is not fully understood. In a recent study, a team of researchers used an energy-based model to identify the […]
Genetically engineered immune cells target cancer cells that may be responsible for leukemia relapse
Genetically modified immune cells successfully target specific cancer cells that may be responsible for the relapse of acute myeloid leukemia (AML). In a study published on 28 April in Nature Communications, the researchers developed a CAR T cell therapy (UCART123) targeting CD123, which is found on leukemia stem cells and enables T cells to seek out […]
PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer | NEJM
Breakthrough findings were presented at the 2022 ASCO Annual Meeting and published in The New England Journal of Medicine by researchers at Memorial Sloan Kettering Cancer Center (MSK) confirming a clinical complete response in all 14 patients who received the immunotherapy treatment dostarlimab as a first-line treatment for mismatch repair-deficient (MMRd) locally advanced rectal cancer. This new approach of “immunoablative” […]
Gene therapy’s comeback: how scientists are trying to make it safer – Nature
It is a pity that non integrating lentiviral vectors are unknown or underused. This is not THE solution but in several cases, I think their use would be more relevant than AAVs use in term of immune response. The advancements of gene therapy will go through the design and development of complementary vector platforms.
CRISPR/Cas9 deletions induce adverse on-target genomic effects
In a recent study, a team of researchers used a CRISPR/Cas9 system to evaluate the use of tRNA by deleting two tRNA genes from the genomes of hyperhepatocellular carcinoma and human chronic myeloid quasi-haploid leukaemia cells. The authors discovered numerous unexpected genomic changes at the target region using an improved droplet-based target enrichment approach followed […]