Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...

Cells convert mechanical forces into biochemical signals through mechanotransduction, a process which can now be synthetically engineered. In this Review, we examine engineered artificial mechanotrans...

Nguyen, Collier et al. find a mitochondria–lysosome inflammatory pathway regulated by the SUMO E3 ligase MAPL, which promotes vesicular mtDNA transport to lysosomes and subsequent gasdermin-dependent ...

UCLA’s three most recent alumni Nobel winners — Fred Ramsdell, Ardem Patapoutian and Randy Schekman — said their experience as Bruins loomed particularly large in their scientific development.

The BioInnovation Institute & Science Prize for Innovation seeks to recognize bold researchers who are asking fundamental questions at the intersection of the life sciences and entrepreneurship. We se...

Nature Reviews Bioengineering, Published online: 13 October 2025; doi:10.1038/s44222-025-00366-7Cells convert mechanical forces into biochemical signals through mechanotransduction, a process which can now be synthetically engineered. In this Review, we examine engineered artificial mechanotransduction mechanisms, from gene circuits responsive to mechanical cues to synthetic force-generating systems that reshape tissue behaviour and cellular function.

A recent study that systematically mapped genomic bindings and regulatory effects of transcription factors (TFs) reported a surprisingly low overlap between TF binding and regulatory targets in Saccha...

Tissue structure, the organization of cells, vasculature and extracellular matrix, determines organ function. Yet how tissue structure changes with aging remains largely unknown. Current aging researc...

Maintaining the dynamic structure of chromatin is critical for regulating the cellular processes that require access to the DNA template, such as DNA …

Despite recent progress in the ability to manipulate the genomes of eukaryotic cells[1][1]–[3][2], there is still no effective and practical method to precisely integrate large synthetic DNA constructs into desired chromosomal sites using a programmable integrase. Serine integrases can perform the necessary molecular steps[4][3], but only if their natural target site is first installed into the recipient genome by other methods. A more elegant approach would be to directly reprogram the serine integrase itself to target a desired genomic site that is different from the natural recognition site of the integrase[5][4]. Here, we describe the development of a Modular Integrase (MINT) platform, a versatile protein-guided genome editing tool that can facilitate site-directed targeted integration (TI) of synthetic DNA into chromosomal sites. Through a combination of structural modeling, directed evolution, and screening in human cells we have reprogrammed the specificity of the serine integrase Bxb1. We demonstrate the therapeutic potential of the MINT platform by retargeting Bxb1 to the human AAVS1 and TRAC loci where wild-type Bxb1 has no detectable activity. By combining the MINT platform with known activity-increasing Bxb1 mutants, we achieved 14% TI at the AAVS1 locus, and by additionally fusing zinc finger DNA binding domains to engineered Bxb1 variants, we achieved 35% TI at the TRAC locus in human K562 cells. To further demonstrate clinical potential, we achieved stable 15% TI of a functional donor construct in human T cells. ### Competing Interest Statement All authors contributed to this work as full-time employees of Sangamo Therapeutics. Sangamo Therapeutics has filed patent applications regarding Integrase systems described in this study, listing F.F., S.A.-F., N.A.S., and J.C.M. as inventors. [1]: #ref-1 [2]: #ref-3 [3]: #ref-4 [4]: #ref-5

Joel Mokyr, Philippe Aghion, and Peter Howitt explained why the last two centuries have seen sustained economic growth rather than stagnation

The Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel 2025 was awarded “for having explained innovation-driven economic growth” with one half to Joel Mokyr “for having identified ...