Model transforms zinc finger design into 'push-button' technology
By applying deep learning methods to a large database of zinc finger nucleases, researchers at the University of Toronto and New York University have developed an algorithm, Zfdesign, that was able to design custom zinc fingers for any given stretch of DNA. “I think this system levels the playing field for zinc fingers and CRISPR,” said Philip Kim, co-corresponding author of the team's paper published online in Nature Biotechnology on Jan. 26, 2023.

Fusion protein has metabolic benefits in mice, macaques
Treatment with the fusion protein QL-1005 reduced caloric intake and body weight in mice and primates. In obese animals, it also improved insulin, fasting glucose and triglyceride levels. The design belongs to the Chinese biopharmaceutical company Beijing QL Biopharmaceutical, which will begin clinical trials in a year.

Model transforms zinc finger design into 'push-button' technology
By applying deep learning methods to a large database of zinc finger nucleases, researchers at the University of Toronto and New York University have developed an algorithm, Zfdesign, that was able to design custom zinc fingers for any given stretch of DNA. “I think this system levels the playing field for zinc fingers and CRISPR,” said Philip Kim, co-corresponding author of the team's paper published online in Nature Biotechnology on Jan. 26, 2023.
Fusion protein has metabolic benefits in mice, macaques
Treatment with the fusion protein QL-1005 reduced caloric intake and body weight in mice and primates. In obese animals, it also improved insulin, fasting glucose and triglyceride levels. The design belongs to the Chinese biopharmaceutical company Beijing QL Biopharmaceutical, which will begin clinical trials in a year.
Other news to note for Jan. 30, 2023
Additional early-stage research and drug discovery news in brief.
Discovery of multitarget inhibitors with anti-inflammatory and analgesic activities
Researchers from Hefei Industrial Pharmaceutical Institute Co. Ltd. presented the discovery and preclinical evaluation of novel multifunctional inhibitors as potential anti-inflammatory and analgesic agents.
ATF3 modulation found as an approach to treat hepatic steatosis
Hepatocellular death is an important process for liver homoeostasis by elimination and replacement of impaired hepatocytes. Hepatocellular death occurs little under normal conditions in the healthy liver, and it plays a key role as a trigger of liver regeneration; meanwhile, hepatic steatosis increases hepatocellular death during liver regeneration, exacerbating both acute and chronic liver damage.
Escient gains IND clearance for first-in-human study of MRGPRX2 antagonist EP-262
Escient Pharmaceuticals Inc. has obtained FDA clearance of its IND application for EP-262, a first-in-class, potent, highly selective small-molecule antagonist of Mas-related G-protein coupled receptor member X2 (MRGPRX2) for mast cell-mediated disorders.

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Conferences

Low CHEK2, ATM and PALB2 expression correlates with better overall survival in CRC
Biomarkers
Outcomes after therapy with DNA-damaging...
CF33-hNIS-antiPDL1 shows efficacy in models of gastric cancer peritoneal carcinomatosis
Cancer
Genetically modified derivatives of the chimeric...
CXCL1 promotes colon cancer progression through NF-κB/P300 activation
Cancer
Upregulation of C-X-C motif chemokine ligand 1 (CXCL1) has been validated in patients with colorectal cancer (CRC), but the mechanism behind CXCL1 affecting CRC tumor cell progression is not clear. Gene-editing techniques were used to investigate the impact of CXCL1 knockout and overexpression in...
GM-CSFR signaling in cholangiocarcinoma and pancreatic ductal adenocarcinoma
Biomarkers
Previous studies have demonstrated that increased expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) correlated with poor prognosis in patients with cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC). In the current study, a research team at the University...

Cancer

Altered plasma proteins tied to progression in castration-resistant prostate cancer
Biomarkers
Androgen deprivation therapy (ADT) is still the main treatment option for locally advanced and metastatic prostate cancer (PCa); however, most patients receiving ADT develop resistance to treatment and relapse, with a more aggressive form of cancer, castration-resistant prostate cancer (CRPC).

Infection

University of Manchester patents new antimicrobials for fungal and bacterial infections
Patents
University of Manchester researchers have...

Chinese Academy of Sciences institutes divulge new compounds for infection and inflammatory disorders
Coronavirus
Shanghai Institute of Materia Medica of the Chinese Academy of Sciences and Wuhan Institute of Virology of the Chinese Academy of Sciences have synthesized amide compounds reported to be useful for the treatment of dengue virus infection, skin inflammation, inflammatory joint disease, inflammatory...
Cas12a2 elicits abortive infection and can be repurposed as an RNA-guided RNA-targeting tool
Drug design, drug delivery and technologies
Bacterial abortive infection is a defense mechanism by which an infected bacterial cell enters dormancy or dies to limit phage replication and protect the clonal population. Recent studies observed that CRISPR RNA-guided adaptive immune systems that target RNA also cause abortive-infection...

Neurology/Psychiatric

Herophilus conducts in vivo studies of HRP-12975 for Rett syndrome
Genetic/Congenital
Herophilus Inc. is conducting in vivo studies of lead candidate HRP-12975, a small-molecule therapy for Rett syndrome, with funding from the Rett Syndrome Research Trust. The company is generating efficacy and safety data with HRP-12975 using genetic mouse models of Rett syndrome.
Lapix receives support from FDA for IND-enabling plan for LPX-TI641
Immune
Lapix Therapeutics Inc. has announced the successful outcome of its pre-IND meeting request with the FDA to achieve alignment on the company's IND-enabling plan for LPX-TI641, being developed for neuro-autoimmune indications such as multiple sclerosis (MS), neuromyelitis optica spectrum disorders...
Inmune Bio uses DN-TNF biologic to target soluble TNF to increase muscle regeneration in DMD model
Inmune Bio Inc., together with a collaborator at University of California, Irvine School of Medicine, has shown targeting soluble TNF (sTNF) using a dominant-negative TNF (DN-TNF) biologic significantly decreased muscle damage in a murine mdx model of Duchenne muscular dystrophy (DMD) and showed a...
NUP50 gene variation tied to ALS risk, researchers find
Biomarkers
Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease, and it is pathologically related with frontotemporal dementia (FTD). Genetic studies have identified C9ORF72 as a major genetic cause of ALS/FTD. Further genetic analyses and validation studies have...
12-Hour as well as circadian brain rhythms disrupted in people with schizophrenia
Research shows that individuals with schizophrenia have abnormal gene expression patterns in their brains compared with people without the condition. In a study published in PLOS Biology on Jan. 24, 2023, the authors reported that many genes in brain tissue from the dorsolateral prefrontal cortex,...

Endocrine/Metabolic

HBM Alpha completes seed financing to advance programs for congenital adrenal hyperplasia and PCOS
Financings
HBM Alpha Therapeutics Inc. has completed seed financing to advance its lead programs, novel antibody therapies to treat congenital adrenal hyperplasia (CAH) and polycystic ovary syndrome (PCOS).

Biomarkers

Plasmatic GAS6 levels predict acute heart failure mortality risk
Cardiovascular
Heart failure still remains a leading cause of death worldwide. Improving risk stratification and prognostic analysis tools is required to aid in the management of the disease.

Study reveals new risk loci for otosclerosis
Ear, Nose and Throat
Otosclerosis affects about 0.3% of population and it is among the most common cause of conductive hearing loss. Otosclerosis is highly familial, with positive family history reported in about 50% to 60% of cases. The disease is characterized by pathologic remodeling of the bone encasing the inner...
Hepsin, IL-8 and OPG as novel blood-based biomarkers in CRC
Conferences
While fecal immunochemical tests (FIT) are common strategies for colorectal cancer (CRC) screening, the potential use of blood-based biomarkers could provide an alternative method to increase compliance in population-based screening programs for early detection of CRC. Researchers from EDP Biotech...

Gastrointestinal

Exegi Pharma cleared to study EXE-346 for management of IPAA patients
FDA
Exegi Pharma LLC has received FDA clearance of its IND application for EXE-346, allowing the company to initiate a clinical trial to evaluate EXE-346 in the management of excessive stool frequency in patients with an ileal pouch-anal anastomosis...
Researchers identify new bacterial species in inflammatory bowel disease
Researchers from University Medical Center Utrecht and Yale University School of Medicine have recently described two novel, strictly anaerobic Allobaculum strains, 128T and 539T, isolated from the feces of humans with inflammatory bowel disease...
Shanghai Leadopharma Technology discloses new TRPA1 antagonists
Patents
Shanghai Leadopharma Technology Co. Ltd. has presented transient receptor potential cation channel subfamily A member 1 (TRPA1) antagonists reported to be useful for the treatment of irritable bowel syndrome, Crohn's disease, ulcerative colitis,...
Researchers report discovery of novel FXR agonists with anti-NASH properties
Researchers from Institute of Medicinal Biotechnology have published details on the discovery of novel nonsteroidal farnesoid X receptor (FXR) agonists as potential therapeutic agents for the treatment of nonalcoholic steatohepatitis (NASH).
Osaka University identifies new PPARα agonists
Patents
Osaka University has presented PPARα agonists reported to be useful for the treatment of nonalcoholic steatohepatitis (NASH).
SFA Therapeutics receives FDA clearance of IND for SFA-001N in NASH and fibrosis
FDA
SFA Therapeutics Inc. has received FDA clearance of its IND application to investigate SFA-001N in patients with nonalcoholic steatohepatitis (NASH) with or without fibrosis.

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