Directed evolution has become a central pillar in gene therapy. This engineering strategy enables the generation of more efficient variants of genetic editors and delivery vectors. Molecular diversification methods are increasingly sophisticated and are now accelerated by machine learning and AI tools, as showcased at the 29th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) held in Boston this week.

Work at Blueprint Medicines Corp. to identify a selective and potent CDK4 degrader led to the identification of BLU-448, with minimal activity against CDK6 for treating HR+/HER2- breast cancer.

Epirium Bio Inc. has developed a series of small-molecule 15-PGDH inhibitors, the phase II-ready MF-300 and preclinical candidate MF-1305, as potential therapeutics for inflammatory bowel disease (IBD).

Resistance to microtubule-targeting agents such as taxanes and vinca alkaloids is often driven by drug efflux and changes in tubulin behavior. Targeting the colchicine-binding site provides an alternative strategy that may circumvent these resistance mechanisms.

Gene therapies rely on vectors to reach the target tissue where they act, such as adeno-associated viruses (AAVs) or lipid nanoparticles (LNPs), among other delivery strategies. Each combination is optimized for a specific cell type and indication, aiming to overcome challenges such as efficacy, specificity and toxicity. On May 13, 2026, two sessions included in the scientific symposia of the 29th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), being held in Boston this week, addressed AAV-related toxicities, which have led to fatal cases in clinical trials and remain an area for improvement in approved therapies.

Mesothelin (MSLN) is a highly expressed protein in several cancer types but with limited expression in normal tissues. Simcere Pharmaceutical Co. Ltd. has presented preclinical data on the characterization of SCR-A019, an antibody-drug conjugate (ADC) carrying a topoisomerase 1 inhibitor payload and an antibody that binds to membrane Mesothelin (MSLN) over soluble MSLN and has shown robust antitumor efficacy in several cell-derived xenograft models.

Researchers from Beacon Therapeutics Holdings Ltd. reported the development of BTX-001, an intravitreal gene therapy designed to target the complement pathway through delivery of a C5 inhibitor.

HEC Pharma Co. Ltd. recently presented HEC-201625, a small-molecule PD-L1 inhibitor for cancer immunotherapy that blocks the PD-1/PD-L1 signaling pathway. HEC-201625 was tested in vitro and in vivo in MC38 syngeneic murine model, as well as in xenograft A375 and NCI-H358 models.

Researchers at Opus Genetics Inc. reported the efficacy of OPGx-BEST1, an AVV-based gene therapy developed to deliver a functional BEST1 transgene to retinal pigment epithelium (RPE) cells to re-establish normal BEST1 expression and activity.