Biology subjects

Saleh, A.

Publications and source records attributed to Saleh, A..

At least 19 recordsLinked to original sources

bioRxiv2026

BRCA2 loss drives a PKM1-dominant glycolytic state that is selectively lethal to pyruvate kinase activation

Homologous recombination deficiency (HRD), most commonly arising from BRCA1/2 loss, is accompanied by metabolic remodeling whose contours and therapeutic implications remain poorly defined. Through pan-cancer analysis of 10,619 tumors from The Cancer Genome Atlas (TCGA) and isogenic BRCA1/2-deficient models, we show that HRD tumors display broad metabolic rewiring, with consistent alterations in glucose metabolism. Unexpectedly, BRCA1/2 loss is associated with selective upregulation of the constitutively active glycolytic enzyme Pyruvate Kinase M1 (PKM1) isoform, contrasting with the PKM2-dominant state of most cancers, and produces an elevated pyruvate kinase activity state. Overactivating PKM, with small molecules activators, including the FDA-approved drug mitapivat, triggers superoxide accumulation, disrupts PINK1-dependent mitochondrial quality control, induces DNA damage, and selectively kills BRCA2-deficient tumors in vivo, while sparing BRCA2-proficient counterparts. These findings recast HRD as a metabolic state and identify PKM activation as a candidate therapeutic strategy for biomarker-selected HR-deficient cancers.

cancer biology↗

bioRxiv2026

The phage shock protein A (PspA) maintains membrane potential and supports NADH dehydrogenase function in mycobacteria

Maintenance of membrane integrity and proton motive force (PMF) is critical for bacterial survival. The phage shock protein (Psp) system, conserved across bacterial species, stabilizes the membrane, maintains PMF, and protects against envelope damage. However, how the conserved effector PspA contributes to PMF maintenance remains unclear. Here, using the mycobacterial Psp system as a genetically tractable model, we provide mechanistic insight into this process. We show that PspA and the accessory protein PspM jointly sustain membrane potential, with PspM required to maintain a ~70 kDa PspA isoform at the membrane during envelope stress. Loss of PspA increases susceptibility to thioridazine, which targets type II NADH dehydrogenase (NDH-2), and to Ro 48-8071, an inhibitor of menaquinone biosynthesis. Notably, hypersusceptibility to thioridazine is rescued by exogenous menaquinone. Consistent with these phenotypes, a pspA-deficient mutant exhibits impaired NADH dehydrogenase activity despite unchanged abundance of NDH-2 and menaquinone (MK-9). Together, these findings identify a functional link between PspA and NADH dehydrogenase-dependent respiration and suggest that PspA contributes to PMF maintenance by supporting respiratory electron transfer.

molecular biology↗

bioRxiv2026

Visualizing zinc-starved slow-replicating Mycobacterium tuberculosis in neutrophil-rich lung lesions

The months-long treatment for tuberculosis is partially attributed to a minor Mycobacterium tuberculosis (Mtb) subpopulation exhibiting phenotypic drug resistance, although origins of these bacilli in hosts remain unknown. Previously, we observed that mycobacteria respond to growth-restrictive limitations of zinc by accumulating Mrf, and inducing Mpy recruitment to the decoding center of the ribosome, thereby hibernating the ribosome in an inactive state. Mrf accumulation - regulated at both transcriptional and post-translational levels by Zur and Clp, respectively, in a zinc-dependent manner - facilitates the formation of stable Mpy-70S ribosome complex in zinc-starved cells. Here, using a translational fusion of Mrf with a fluorescent-reporter protein we visualized zinc-starved mycobacteria with a physiology conducive for Mpy-dependent ribosome hibernation. About half of zinc-starved mycobacterial population expressed microscopically detectable levels of the reporter and exhibited Mpy-dependent slowdown of growth and isoniazid tolerance in vitro. In chronic, high-burden mouse lung infections, ~3% of Mtb bacilli expressed the reporter, and the frequency increased to ~35% upon isoniazid treatment. Transcriptomics of mouse lungs suggests an important role of S100A8/A9 and ZIP2 in neutrophils in zinc mobilization during Mtb infections. Moreover, depletion of neutrophils, or loss of S100A9 caused significant attenuation of zinc starvation response in Mtb. Altogether, the study offers a new approach for visualizing and manipulating slow-replicating Mtb in host tissues.

microbiology↗

bioRxiv2026

Compact type II-D Cas9 nucleases for efficient and specific genome editing

Compact CRISPR nucleases are attractive for therapeutic genome editing because their small coding sequences facilitate delivery by adeno-associated virus. Type II-D Cas9 (Cas9d) enzymes constitute the most compact Cas9 subtype, yet only a few orthologs have demonstrated mammalian genome-editing activity, leaving it unclear whether this activity is general or exceptional. Here, we mined the IMG/M metagenomic database and identified five previously uncharacterized MG102-like Cas9d orthologs ([~]950 amino acids) that share the hallmark genomic, sequence, and structural features of type II-D Cas9. Two of them, Cas9d-1 and Cas9d-4, recognized a 5-NRC-3 protospacer-adjacent motif and edited endogenous human loci with efficiencies up to 20.1%, exceeding Streptococcus pyogenes Cas9 at one site, while producing deletion-biased outcomes and no detectable off-target activity. Notably, both orthologs edited more efficiently than the sole previously validated member of this lineage, MG102-2, when assayed side by side under identical conditions. These findings establish compact MG102-like Cas9d orthologs as robust and specific genome editors and provide promising, single-AAV- compatible scaffolds for in vivo therapeutic genome editing.

bioengineering↗

bioRxiv2026

Compact type II-C Cas9 nucleases with expanded PAM access and high fidelity for therapeutic genome editing

Compact type II-C Cas9 nucleases are attractive for therapeutic genome editing because their small size enables packaging into adeno-associated viral (AAV) vectors, and their extended protospacer-adjacent motifs (PAMs) reduce off-target cleavage while expanding targeting scope. Yet characterized type II-C orthologs have edited mammalian cells far less efficiently than the canonical SpCas9. Here, we used embedding-based metagenomic mining of >4.7 x 10 proteins, combined with AlphaFold3 structure prediction and locus-context analysis, to identify three previously uncharacterized compact type II-C Cas9 orthologs, NsuCas9 (1,092 aa), PsuCas9 (1,084 aa), and GfoCas9 (1,074 aa), and benchmarked them in vitro and in human HEK293T cells. All three are robust RNA-guided nucleases with distinct PAM specificities (N CC, N NYAA, and N RHAA, respectively), divergent thermal profiles, and asymmetric sgRNA cross-compatibility. In human cells, PsuCas9 with an N ATAA PAM reaches 78.4% indels and matches or exceeds SpCas9 at multiple loci, representing the first natural compact type II-C ortholog reported to do so, while GfoCas9 and NsuCas9 add complementary coverage. All three show a strong deletion-biased repair signature and no detectable editing across 33 predicted off-target sites. These compact, high-fidelity nucleases expand the CRISPR targeting space for AAV-deliverable therapeutic editing.

bioengineering↗

bioRxiv2026

Single anticodon-edited tRNA therapy targeting highly prevalent Arg>Ter premature termination codons causing inherited retinal diseases

Nonsense variants cause 18% of inherited retinal diseases (IRDs), yet current therapies require variant-specific development, leaving most patients untreated. Here, we combined a large-scale genetic analysis literature survey of >37,500 IRD patients with anticodon-edited (ACE)-tRNA engineering to create a single, gene-agnostic therapy targeting Arg>Ter nonsense variants which are the most prevalent subclass (35%) of premature stop codons (PTCs). We developed an optimized ACE-tRNA (V3) that achieved up to 86% readthrough across 13 clinically relevant variants, restored native PRCD localization in the arRP-causing p.R22* mutant, and demonstrated activity in photoreceptor-like cells. To enable translation, we established an AAV2/7m8 production platform (1*10{superscript 1}{superscript 2}-1*10{superscript 1}3 GC/mL) and defined 1*10 GC/eye as the safe dose in mice. This patient genetics-guided strategy positions ACE-tRNA_V3 as a promising candidate for preclinical development, offering a precision medicine approach that targets the most common nonsense variant class with a single therapeutic molecule.

genetics↗

bioRxiv2026

Integrated multi-omics profiling of gut bacterial extracellular vesicles links cargo composition to host transcriptional responses

Bacterial extracellular vesicles (bEVs) enable gut microbiota to deliver bioactive cargo to host cells, yet the specific bacterial producers have not been systematically identified. Here, we profiled stool-derived bEVs from healthy individuals using metaproteomic profiling, revealing that vesiculation is widespread across gut bacterial phyla. We selected a subset of vesiculating species, showing that bEVs localize to distinct tissues in vivo, including extraintestinal sites such as lung, liver, kidney, and bone, suggesting roles beyond the gastrointestinal tract. We profiled intestinal epithelial cells and macrophages after endocytosing bEVs from various species, uncovering pronounced, cell-type-specific responses. For example, Bacteroides fragilis bEVs promote anti-inflammatory mitochondrial-telomeric regulation, while a set of commensal-derived bEVs contribute to epithelial survival and structural renewal. By combining proteomic, lipidomic, and metabolomic cargo profiling with transcriptional output, we find that specific Bacteroidota-derived protein cargo activates cytoprotective stress defenses while attenuating inflammatory signaling. Together, these findings establish a multi-layered comparative atlas of bEV composition, uptake, and host response, providing a framework for understanding bEV-mediated microbiome-host communication.

microbiology↗

bioRxiv2026

Inorganic sulfate transport by the Mycobacterium tuberculosis PE22/PPE36 complex

Mycobacterium tuberculosis (Mtb) encodes two multigene families with 169 members that are exclusive to mycobacteria, the pe and ppe genes. These genes have unusual sequences including low-complexity repeat regions, but their functions--and whether they share a common function--have long been unclear. Recently, several members of the pe/ppe family were shown to transport nutrients across the outer Mtb membrane, a role for which no other proteins have yet been identified. Whether nutrient transport is a family-wide function and the range of nutrients transported by the PE/PPEs remains unclear. Sulfur is an essential nutrient for Mtb physiology and pathogenesis. To test whether PE/PPE transporters contribute to sulfur acquisition, we analyzed the transcriptional response of Mtb to sulfate by RNA sequencing. The pe22/ppe36 genes were induced in sulfate-limiting conditions. Deletion of pe22/ppe36 impaired growth in low-sulfate media and reduced intracellular sulfate levels, effects that were reversed by heterologous expression of the Mycobacterium smegmatis porin MspA. The response of sulfur-responsive genes to sulfur was muted in the pe22/ppe36 deletion strain, and mass spectrometry showed lower sulfolipid and sulfur metabolite levels in the deletion strain. These findings identify PE22/PPE36 as a specific sulfate uptake system and supports the emerging idea of PE/PPE proteins as nutrient uptake systems across the Mtb outer membrane. Significance statementThe mechanism of nutrient transport across the porin-less mycobacterial outer membrane and the function of the large pe/ppe gene family have been longstanding questions in mycobacterial biology. This study shows that the Mycobacterium tuberculosis PE22/PPE36 complex serves as a selective conduit for inorganic sulfate. Deletion of this complex disrupts intracellular sulfur homeostasis and triggers a metabolic seesaw that depletes cell-surface sulfolipids. Our findings expand the PE/PPE transport paradigm and suggest a direct link between nutrient acquisition and TB transmission.

microbiology↗

bioRxiv2026

Metabolic control of drug resistance by a mycobacterial ion channel

Pyrazinamide (PZA) is a cornerstone of modern tuberculosis therapy, yet its context-dependent activity has obscured both its mode of action and resistance mechanisms. Using a host-mimicking culture system integrated with genome-wide CRISPRi profiling, metabolomics, and comparative genomics, we identify a previously unrecognized driver of PZA resistance in humans: loss of the ion channel Rv2571c. Rv2571c mediates -ketoglutarate efflux, amplifying PZA-induced cytoplasmic acidification under host-relevant acidic conditions. Loss-of-function mutations confer resistance in vitro and in vivo and are under positive selection in clinical isolates, establishing this pathway as a resistance determinant in patients. Together, these findings define a novel, ion channel-mediated resistance mechanism, establish cytoplasmic acidification as the basis of PZA killing, and inform resistance detection and treatment-shortening drug development.

microbiology↗

bioRxiv2025

Dormant viral pathways underlie space-induced neural senescence: a neuroprotective strategy for spaceflight and neurological diseases

Long-duration spaceflight is associated with neurological symptoms in astronauts, yet the underlying molecular mechanisms remain unclear. Using human brain organoids cultured aboard the International Space Station, we analyzed three independent spaceflights to demonstrate that exposure to the space environment triggers Space-Induced Neural Senescence (SINS), characterized by chromatin remodeling, mitochondrial dysfunction, and activation of viral-like transcriptional programs in the absence of infection. Multi-omics analyses identified upregulation of endogenous LINE-1 (L1) retroelements, whose activity was markedly enhanced in organoids lacking MECP2, a known L1 repressor implicated in Rett syndrome. The resulting accumulation of cytoplasmic L1 DNA elicited an IL-6-mediated inflammatory and neurotoxic response, which was reversed by reverse transcriptase inhibitors (RTi) such as lamivudine or stavudine. Parallel preclinical experiments in Mecp2-deficient mice confirmed that RTi treatment restored neuronal morphology, synaptogenesis, function, cognition, and survival. These findings reveal that the space environment reactivates dormant genomic retroelements, providing an unexpected mechanistic insight into astronaut neurobiology and identifying a potential therapeutic strategy for both space-induced and terrestrial neurological conditions. Our pioneering study demonstrates the value of space-enabling research in accelerating drug discovery and disease treatment on Earth.

neuroscience↗

bioRxiv2025

Characterization and engineering of highly efficient Cas12j genome editors

The large size of CRISPR-Cas enzymes limits their delivery for therapeutic applications. Cas12j nucleases offers hypercompact alternative but show moderate editing efficiency. To overcome this limitation, we identified eight novel Cas12j orthologues (Cas12j-11 to Cas12j-18) from viral metagenomes. All showed low editing activity in mammalian cells. We engineered T5 exonuclease-Cas12j fusions (T5Exo-Cas12j), two of which, T5Exo-Cas12j-12, and -18 exhibited up to 42% editing in HEK293T and 9% in K-562 cells, outperforming wild-type Cas12j counterparts and comparable to LbCas12a. Intriguingly, robust in cellula editing in both HEK293T and K-562 cells was strictly dependent on the presence of 5'-TAC trinucleotides within the target DNA sequence. Furthermore, we fused the Cas12j orthologues with the TadA8e deaminase and developed base editors, termed Be-(d)Cas12j. Among these, Be-(d)Cas12j-13 demonstrated efficient A-to-G base conversion in mammalian cells. This study expands the CRISPR toolbox by characterizing and engineering novel Cas12j orthologues into compact, high-efficiency genome editors.

bioengineering↗

bioRxiv2025

Epigenetic inheritance of complex learning abilities in the mammalian brain

For several decades, the question of whether cognitive and learning capacities can be inherited through non-genetic mechanisms has been the subject of ongoing debate. Here, we provide the first evidence of transgenerational inheritance of enhanced ability to learn complex tasks in the mammalian rodent brain. These inherited learning enhancements are not limited to specific stimuli, sensory modalities, or learning paradigms. Using behavioral, cellular biophysical, methylomics, genetics and molecular methods, we find that the inherited epigenetic modifications reflect an enhanced neuronal learning state, driven by increased intrinsic neuronal excitability in most pyramidal neurons in the relevant neuronal networks. This enhancement is mediated by persistent downregulation of the muscarinic M-current and is associated with widespread changes in DNA methylation, notably within coding genes associated with the M-current, the Kv7 pathway, in the hippocampi of trained F0 rats, as well as in non-coding RNAs in their sperm samples. Remarkably, a significant portion of these DNA methylation changes were also observed in the hippocampi of their untrained F1 offspring. These findings suggest that complex learning abilities can be inherited in the mammalian brain, as the offspring of trained rodents are born with the biophysical modifications that enable them to become super-learners, the exact change that occurs in their parents brains only after the rule learning.

neuroscience↗

bioRxiv2025

A 3-genes interferon signature predicts sustained complete remission in pediatric AML patients

The immunological composition of the microenvironment has shown relevance for diagnosis, prognosis, and therapy in solid tumors but remains underexplored in acute leukemias. We investigated the significance of acute myeloid leukemia (AML) bone marrow microenvironment in predicting chemosensitivity and long-term remission in pediatric patients. We analyzed 32 non-promyelocytic pediatric AML patients at diagnosis using NanoString PanCancer IO 360 assay, RNA sequencing, and deep-phenotype flow cytometry analyses. The findings were validated using the pediatric TARGET AML dataset. A short signature of three interferon (IFN)-related genes (GBP1, PARP12, TRAT1) distinguished patients with chemosensitive disease and reduced minimal residual disease after induction chemotherapy. The signature stratified patients overall, and within the clinically defined "standard-risk" group, patients with high gene expression at diagnosis had significantly longer overall survival. The leukemia microenvironment associated with this signature showed enrichment of non-exhausted CD4+ and CD8+ T cytotoxic lymphocytes and expansion of CD8+ T effector memory cells re-expressing CD45RA (TEMRA) in patients with a favorable prognosis. Our results show the importance of the bone marrow microenvironment in pediatric AML and provide tools for a refined stratification of "standard-risk" patients, lacking adequate risk-oriented therapies. They also offer a promising guide for tackling immune pathways and exploiting immune-targeted therapies. Statement of significanceWe identified a novel three-gene IFN-related signature that distinguished pediatric AML patients by chemosensitivity and remission outcomes. It stratified patients across all risk groups, including the "standard-risk" group, with high expression linked to a T-cell-enriched microenvironment and longer survival. This signature may enhance risk stratification and guide targeted immunotherapy.

cancer biology↗

bioRxiv2025

Integrated genetic screening reveals FEN1 as a driver of stemness and temozolomide resistance in glioblastoma

Glioblastoma (GBM) is a lethal brain tumor with limited response to standard of care chemoradiotherapy. In this study, we conducted genome-wide CRISPR knockout screening in patient-derived glioblastoma stem cells (GSCs) to identify genetic dependencies of cell survival and therapy resistance. Our screening identified flap endonuclease 1 (FEN1) as a key driver of GSC survival, with enhanced dependency under temozolomide (TMZ) treatment. Genetic perturbation of FEN1 reduced GSC self-renewal and proliferation in vitro, and prolonged survival in a patient-derived xenograft model of GBM. FEN1 inhibition (FEN1i) preferentially affected highly aggressive or recurrent GBM models compared with less aggressive GBMs and healthy neural stem cells. Moreover, FEN1 inhibition synergized with TMZ only in these aggressive FEN1i-sensitive GSCs, providing cancer-selective killing and TMZ sensitization in the most untreatable of GBMs. Mechanistically, FEN1i-sensitive GSCs exhibited greater proliferation and sphere formation, while stalling their proliferation conferred resistance to FEN1 inhibition. Single-cell transcriptomics further linked FEN1 expression to stemness and the DNA damage response, elucidating broader determinants of FEN1 dependency. These findings establish FEN1 as a promising therapeutic target in GBM, offering a strategy for both selective targeting and enhancement of TMZ efficacy in aggressive cancers. Statement of SignificanceThis study identifies FEN1 as a key vulnerability of glioblastoma stem cells, revealing its role in therapy resistance and stemness, and proposes FEN1 inhibition as a strategy to enhance temozolomide efficacy.

cancer biology↗

bioRxiv2025

SLFN11 Enhances Cisplatin Sensitivity in Pediatric Cancer via Activation of Stress-Response and Suppression of Survival Pathways

Pediatric cancers pose significant treatment challenges due to their biological heterogeneity and variable responses to chemotherapy. SLFN11, a DNA/RNA helicase-like protein known to sensitize adult tumors to DNA-damaging agents, remains underexplored in pediatric malignancies. Here, we investigate the role of SLFN11 across pediatric Wilms tumor, osteosarcoma, and medulloblastoma using integrated bioinformatics, epigenetic profiling, and functional assays. In silico analysis of TARGET and ICGC datasets revealed distinct correlations between SLFN11 expression and patient survival, with positive, negative, or neutral predictive value depending on tumor type. Baseline expression and promoter methylation analysis in pediatric cancer cell lines demonstrated epigenetic regulation of SLFN11, similar to adult cancers. Using CRISPR-dCas9-mediated activation, we successfully upregulated SLFN11, which significantly enhanced sensitivity to cisplatin and the PARP inhibitor talazoparib across all tested cell lines. Transcriptomic profiling under cisplatin treatment indicated that SLFN11 modulates DNA damage response and MAPK signaling pathways, potentially contributing to chemotherapy sensitivity. These findings establish SLFN11 as a context-dependent predictive biomarker and a potential therapeutic target to overcome chemoresistance in pediatric solid cancers.

cancer biology↗

bioRxiv2025

Desiccation-induced DNA damage facilitates drug resistance in Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) is an obligate human pathogen that depends on its ability to spread from host-to-host to survive as a species. Yet, knowledge of transmission-specific traits remains lacking. Here, we report the discovery of a specific adaptive response to desiccation, a stress intrinsically linked to the generation of the aerosol droplets within which Mtb transmits. We show that desiccation inflicts oxidative damage and activates Mtbs DNA repair responses but that this repair is imperfect and results in mutations. We further show that activation of these DNA repair responses is accompanied by increased expression of the transcription-coupled repair factor, mfd, but that this expression serves to buffer the fitness cost of specific resistance-conferring mutations in rpoB, the target of the frontline drug rifampin, rather than to facilitate transcription-coupled DNA repair. Silencing mfd during aerosolization impairs survival of strains harboring the rifampin resistance allele S450L. This function is further supported by whole genome sequence data from over 50,000 clinically circulating strains. These studies indicate that Mtb has evolved transmission-specific stress responses that have enabled it to leverage desiccation-induced DNA damage as a potential source of genetic diversification and drug resistance.

microbiology↗

bioRxiv2025

Alcohol Use Disorder Associated Gene FNDC4 Alters Glutamatergic and GABAergic Neurogenesis

Large-cohort genome-wide association studies (GWAS) for alcohol use disorder (AUD) and AUD-related phenotypes have identified more than one hundred genetic loci. Functional study of those GWAS-identified loci might represent an important step toward understanding AUD pathophysiology. We found that genetic loci which are splicing quantitative trait loci (sQTLs) for the fibronectin III domain containing 4 (FNDC4) gene in the brain were identified by GWAS for both AUD drug treatment outcomes and AUD risk. However, FNDC4 function in the brain and how it might contribute to AUD pathophysiology remain unknown. In the present study, we characterized GWAS locus-associated FNDC4 splice isoforms, studies which suggested that FNDC4 alternative splicing results in loss-of-function for FNDC4. We also investigated FNDC4 function using CRISPR/cas9 gene editing, and the creation of human induced pluripotent stem cell (iPSC)-derived neural organoids joined with single-nucleus RNA sequencing. We observed that knock-out (KO) of FNDC4 resulted in a striking shift in the relative proportions of glutamatergic and GABAergic neurons in iPSC-derived neural organoids, suggesting a possible important role for FNDC4 in neurogenesis. We also explored potential mechanism(s) of FNDC4-dependent neurogenesis with results that suggested a role for FNDC4 in mediating neural cell-cell interaction. In summary, this series of experiments indicates that FNDC4 plays a role in regulating cerebral cortical neurogenesis in the brain. This regulation may contribute to the response to AUD pharmacotherapy as well as the effects of alcohol on the brain.

genomics↗

bioRxiv2024

Fusions of catalytically inactive RusA to FokI nuclease coupled with PNA enable programable site-specific double-stranded DNA breaks

Programmable site-specific nucleases have revolutionized the genome editing. However, these systems still face challenges such as guide dependency, delivery issues, and off-target effects. Harnessing the natural functions of structure-guided nucleases offer promising alternatives for generating site-specific double-strand DNA breaks. Yet, structure-guided nucleases require precise reaction conditions and validation for in-vivo applicability. To address these limitations, we developed the PNA-Coupled FokI-(d)RusA (PC-FIRA) system. PC-FIRA combines the sequence-specific binding ability of peptide nucleic acids (PNAs) with the catalytic efficiency of FokI nuclease fused to a structurally-guided inactive RusA resolvase (FokI-(d)RusA). This system allows for precise double-strand DNA breaks without the constraints of existing site-specific nuclease and structure-guided nucleases. Through in vitro optimizations, we achieved high target specificity and cleavage efficiency. This included adjusting incubation temperature, buffer composition, ion concentration, and cleavage timing. Diverse DNA structures, such as Holliday Junctions, linear, and circular DNA, were tested demonstrating the potential activity on different target forms. Further investigation has revealed the PC-FIRA system capacity for facilitating the precise deletion of large DNA fragments. This can be useful in cloning, large-fragment DNA assembly, and genome engineering, with promising applications in biotechnology, medicine, agriculture, and synthetic biology.

bioengineering↗