搜索结果：Biomolecules & therapeutics

Biotherapeutic antibodies are increasingly being developed and, various strategies have recently been used to maximize their potential therapeutic efficacy. The crystallizable fragment (Fc) region of therapeutic monoclonal antibodies (mAbs) is often engineered to tailor their effector functions and pharmacokinetic (PK) properties by introducing point mutations. Notably, most of these mutations are in the hinge and constant domains of the heavy chain, which may silence antibody effector functions. Several liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods have been published to quantify biotherapeutics with a canonical human Fc portion. This work presents a rapid and sensitive hybrid immunocapture liquid chromatography-tandem mass spectrometry (IC-LC-MS/MS) method for quantifying total antibody concentration, specifically targeting the LALA-mutated peptide (L234A/L235A). The sample preparation process, which includes immunocapture, as well as trypsin and Glu-C digestion, is efficiently completed within two days through automation. The developed method was validated according to the ICH M10 guideline and white papers recommendation, focusing on the following parameters - accuracy, precision, dilution linearity, selectivity, stability, recovery- and using a humanized IgG1 LALA-mutated antibody, teplizumab, as analytical standard. The method demonstrated linearity for total antibody detection in mouse plasma samples, with a dynamic range from 150 ng/mL (lower limit of quantification, LLOQ) to 15,000 ng/mL (upper limit of quantitation, ULOQ). All validation parameters tested in mouse plasma met the predefined acceptance criteria, demonstrating the method's reliability and robustness. Additionally, the qualified method was successfully used to characterize the pharmacokinetic profile in mice of an antibody-drug conjugate (ADC-1) containing the LALA mutation in its Fc region. This work provides a valuable foundation for the quantification of new biological entities (NBEs) and antibody-drug conjugates (ADCs) in pharmaceutical development, as it enables the measurement of engineered Fc biotherapeutics using a unique and highly selective peptide, irrespective of the type of biological matrix and even in the presence of other biomolecules of similar IgG isotype.

Biomolecular condensates formed through liquid-liquid phase separation (LLPS) are widely regarded as a fundamental mode of cellular organization. Many intractable diseases, including cancer and neurodegenerative disorders, are increasingly linked to dysregulated biomolecular condensates. Aberrant condensates can serve as phenotypic markers for discovering drugs that target these challenging diseases. In this review, we discuss three main approaches for identifying hit compounds that modulate LLPS: condensate phenotype-based screening, compound repurposing, and rational design. We also highlight the importance of understanding LLPS mechanisms and their central role in guiding drug discovery and optimization. Despite the many remaining challenges, condensate-based drug discovery represents a highly compelling paradigm for next-generation therapeutics.

Extracellular vesicles (EVs) have become key mediators of intercellular communication in melanoma cells and significantly affect disease progression by delivering bioactive molecules. EVs are loaded with a wide variety of biomolecule carriers, including proteins, DNA, mRNAs and non-coding RNAs, which can affect processes such as tumour growth, metastasis, angiogenesis, drug resistance and immune escape. Melanoma-derived EVs dynamically reshape the tumour microenvironment (TME) by regulating different cellular components, such as cancer-associated fibroblasts (CAFs), endothelial cells, T cells, macrophages and natural killer (NK) cells. In addition, we emphasize the enormous potential of EVs as minimally invasive biomarkers for diagnosis, prognosis prediction and treatment monitoring. The biocompatibility and targeting characteristics of EVs also make them promising platforms for drug delivery, including as carriers for chemotherapy drugs and immunomodulators. In this review, we emphasized the key role of EVs in melanoma and their dynamic regulation of microenvironment components, providing new diagnostic and therapeutic approaches for the use of EVs in the treatment of invasive malignant tumours. HIGHLIGHTS: Melanoma-derived EVs carry diverse biomolecules that reprogram the tumor microenvironment. EVs mediate immune escape, drug resistance and metastasis via key signaling pathways. EVs serve as minimally invasive liquid biopsy biomarkers for diagnosis, prognosis, and therapy monitoring. Engineered EVs offer promising platforms for targeted drug delivery and immunotherapy in melanoma.

Site-specifically attaching biorthogonal handles to proteins is an essential tool for chemical biology research and diverse applications, including imaging, protein immobilization, and the development of next-generation therapeutics such as antibody drug-conjugates. Among the available strategies, enzymatic post-translational modification of short protein tags offers precision, stability, and modularity. However, complex substrate syntheses, the requirement of long recognition tags, and limited reaction efficiencies pose remaining limits for application. Here, we present ADDing, a straightforward enzymatic method for functionalizing proteins with click chemistry handles using the flavin transferase ApbE. We discovered that, given a dedicated adenine diphosphate derivative (ADD) substrate, ApbE attaches a phosphoribosyl moiety bearing bioorthogonal handles to DxxxGAT amino acid motifs. ADDing benefits from a streamlined workflow, due to simple enzymatic substrate synthesis from NAD+ and inexpensive precursors, allowing one-pot click handle generation and protein conjugation. ADDing enables rapid, high-yield functionalization of proteins featuring the recognition tag at either terminus or internal loops, and is compatible with copper and copper free azide-alkyne cycloaddition. We demonstrate its broad applicability in a wide variety of protein functionalizations, including fluorescent labeling, protein-protein, protein-DNA conjugation, and protein immobilization. This versatile technology thus holds great potential for chemical biology and therapeutic development.

Therapeutic biomolecules are widely used to treat various diseases, but their clinical efficacy is often limited by short in vivo half-lives due to rapid renal filtration, proteolytic degradation, and immune clearance. Short half-life leads to frequent dosing, fluctuation in blood drug concentration, and increased treatment costs, severely limiting clinical efficacy. To address these challenges, various half-life extension strategies have been developed, including chemical conjugation (e.g., PEGylation), physical delivery systems (e.g., microspheres), and genetic/fusion approaches. This review provides a comprehensive narrative analysis of molecular engineering methods, discussing the rational design to directly optimize the drug molecule itself or fuse it with long-acting carriers to significantly extend its circulation time. A systematic comparison of several approaches is presented to guide rational strategy selection. By synthesizing current knowledge and recent advances, this review serves as a practical resource for researchers and drug developers navigating half-life extension technologies.

Dynamic and programmable control of therapeutic delivery is a long-standing goal in medicine. Iontronic devices offer precise electronic control over the dosage of bioactive molecules, yet their use has been confined to charged, low-molecular-weight compounds that are electrochemically stable during transport. Here, we present a hybrid delivery platform that integrates iontronic transport with bioorthogonal click-to-release chemistry. In this system, iontronic pumps electrophoretically deliver charged tetrazines as molecular scissors that selectively react with immobilized trans-cyclooctene (TCO)-linked payloads, enabling on-demand bioorthogonal cleavage of the TCO linker and controlled payload release. This approach retains the electronic precision of iontronics while overcoming molecular size, charge, and stability constraints. We demonstrate tunable tetrazine delivery over several days and electronically controlled release of immobilized payloads from small bioactive molecules, such as the antimitotic agent CA4, to the large protein bovine serum albumin. Hence, by integrating bioorthogonal click-to-release strategies, iontronic delivery is extended to biologically relevant macromolecules, providing a foundation for advanced programmable electroceutical devices.

Peptides and proteins are the most dynamic class of biomolecules, performing a diverse range of physiological functions including biochemical catalysis, ion transport, molecular signaling, and genetic/epigenetic regulation and expression. Considering their indispensable functionality and tremendous diversity, peptide and protein related diseases present both an enormous challenge to human health and a valuable opportunity for therapeutic development. Unfortunately, peptide and protein therapeutics are susceptible to proteolytic degradation and often exhibit poor membrane permeability. Moreover, renal clearance, short circulation time, low plasma stability, and immunogenicity are persistent challenges for delivery. Due to inherent lability in the GI tract and poor absorption and permeability through membranes, the majority of FDA-approved peptide and protein therapeutics are approved for parenteral delivery. However, molecular engineering, drug carriers, and/or co-formulations with effective agents may be used to enhance drug delivery and enable use of more attractive administration routes. This review catalogues and describes established and emerging strategies for chemical and structural modification, formulation, and administration of peptide and protein therapeutics, additionally analyzing how such strategies and technologies have influenced scientifically ground-breaking and commercially successful therapies in the modern market.

Delivery of biomolecules into plant vascular tissues remains a barrier to managing diseases caused by insect vector-borne pathogens and to modifying phenotypes of established perennial crops. Inspired by the vascularized growth of crown galls induced by Agrobacterium tumefaciens, we repurposed the bacterium's plant growth regulator (PGR) genes to engineer autonomously dividing, transgene-expressing plant cell structures termed symbionts. A plant transformation vector (pSYM) incorporating the IaaM, IaaH, Ipt and gene5 cassette from A. tumefaciens strain C58 together with a gene of interest on the same transfer DNA was delivered to stems of herbaceous and woody dicots using disarmed A. tumefaciens strain EHA105. Symbiont morphology, vascular differentiation, transgene expression, molecular mobility and protein secretion were evaluated using microscopy, fluorescent reporters, dye tracing, RNA silencing assays and mass spectrometry-based proteomics. pSym inoculation reproducibly generated symbionts across diverse host plant species that were vascularly integrated into their host plants and transgene expression ranging from heterogeneous niches to more uniform patterns. Small molecules moved between symbionts and host vascular tissues, whereas larger proteins exhibited more restricted mobility. Post-transcriptional gene silencing signals moved freely throughout the symbiont and slightly into adjacent stem tissue. Under tested field and greenhouse conditions in potato and tomato, respectively, gall or symbiont formation had no negative impacts on plant growth or tuber and fruit yield. In vitro, symbiont cultures abundantly secreted recombinant protein into surrounding media. Together, these results establish symbionts as a modular, plant bioengineering platform capable of producing and potentially delivering biomolecules without modifying the host plant genome, providing a foundation for vascular-targeted therapeutics and phenotype modulation in crops.

Antibody-derived bioconjugates have emerged as practical biomolecules for applications in diagnostics and therapeutics. A key challenge is achieving site-selective bioconjugation to preserve the native function of the labeled biomolecule. Methods that target native amino acid residues can broaden the applicability of bioconjugates; however, most existing methods rely on genetically engineered antibodies to ensure site-specific labeling. In this report, a chemoenzymatic strategy for modifying a native Fab fragment derived from trastuzumab was investigated using the EzMTG-pG fusion protein, which consists of a microbial transglutaminase variant and protein G. To mitigate the hydrophobic nature of the widely used dibenzocyclooctyne (DBCO) moiety for click chemistry, a new DBCO-containing glutamine donor peptide (DBCO-PEG4-LLQG) was designed. This substrate peptide enabled Lys65-selective conjugation of the Fab via EzMTG-pG catalysis, achieving a 92% modification rate within 4 h. The subsequent click reaction between the Fab-DBCO conjugate and an azide-bearing fluorescent small molecule probe generated a Fab-fluorophore conjugate that retained cell-specific binding to a target cell line. These results demonstrate that the chemoenzymatic pathway, using EzMTG-pG catalysis combined with a click reaction, provides a versatile approach for generating Fab-based bioconjugates with potential applications in diagnostics and therapeutics.

The blood-brain barrier (BBB) is a highly selective and dynamic neurovascular interface essential for maintaining central nervous system homeostasis. This specialized barrier comprises brain microvascular endothelial cells interconnected by tight junctions, supported by pericytes and astrocytic end-feet within the neurovascular unit. While protecting the brain from circulating pathogens and toxins, the BBB presents formidable obstacles to drug delivery, restricting approximately 98% of small-molecule therapeutics and nearly all large biomolecules from reaching the brain parenchyma. BBB dysfunction is critically implicated in the pathogenesis and progression of numerous neurological disorders, including ischemic stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and brain tumors. This comprehensive review systematically examines the structural organization and functional characteristics of the BBB, elucidates its pathophysiological roles across major neurological diseases, and critically evaluates innovative drug delivery strategies designed to overcome this biological barrier. We analyze passive targeting approaches, active targeting mechanisms via receptor-mediated transcytosis, and stimuli-responsive systems including focused ultrasound and magnetic guidance. Additionally, we discuss multifunctional nanoplatforms, biomimetic cell membrane-coated delivery systems, current preclinical evidence, and clinical translation challenges. Finally, we propose future research directions and identify specific experimental pathways to accelerate the development of next-generation BBB-targeted therapeutics from preclinical promise to clinical application.

Small extracellular vesicles (sEVs) are naturally secreted nanovesicles that mediate intercellular communication by transporting biomolecules such as proteins and nucleic acids. Their inherent biocompatibility makes them promising platforms for RNA therapeutics; however, efficient encapsulation of small RNAs remains challenging. To address this, we developed the Protein N-Myristoylation-induced sEVs Loading (PMEVL) system. PMEVL employs a genetic construct encoding an N-Myristoylation peptide and, optionally, a small-RNA expression cassette in its 3'-untranslated region, enabling N-myristoylation-dependent, efficient, and specific RNA loading into sEVs. Mechanistically, PMEVL enhances sEVs biogenesis by activating ERK1/2 and inhibiting AMPK, while promoting RNA loading through recruitment of ANXA2 and key ESCRT components ALIX and TSG101. This system achieved highly efficient encapsulation of diverse functional RNAs, including exogenous/endogenous small RNAs (miRNAs, siRNAs) and messenger RNAs (e.g., GFP, mCherry), as well as co-loading of multiple siRNAs with proteins of interest. To demonstrate therapeutic potential, PMEVL-mediated delivery of Pcsk9 siRNA suppressed hepatic Pcsk9 expression in vitro and in vivo. In C57BL/6 mice, this treatment restored hepatic low-density lipoprotein receptor (LDLR) expression and significantly reduced serum levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol, without systemic toxicity. Furthermore, systematic screening of 181 peptides representing the N-terminal 15-18 residues of human N-myristoylated proteins identified candidates that substantially enhanced PMEVL loading efficiency. Collectively, PMEVL represents a versatile, efficient, and modular platform for loading RNA therapeutics into sEVs, with demonstrated co-loading capability for proteins in vitro.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive failure, memory impairment, and behavioral disturbances. The disease is associated with complex pathological mechanisms including amyloid-β (Aβ) plaque deposition, tau hyperphosphorylation, oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Despite extensive research, currently available therapeutic options provide only symptomatic relief and fail to halt disease progression. Consequently, increasing attention has been directed toward natural bioactive compounds with multi-target therapeutic potential. Marine ecosystems represent a vast reservoir of structurally unique biomolecules, among which marine-derived polysaccharides have emerged as promising candidates for neuroprotection. Polysaccharides such as fucoidan, alginate, carrageenan, chitosan, ulvan, chondroitin sulfate, and hyaluronic acid exhibit diverse biological activities, including antioxidant, anti-inflammatory, anti-amyloidogenic, and neuroprotective effects. These biomolecules can modulate several critical intracellular signaling pathways implicated in AD pathology, including the NF-κB, MAPK, PI3K/Akt/GSK-3β, Nrf2/ARE, STAT3, and NLRP3 inflammasome pathways. By regulating these pathways, marine polysaccharides can reduce oxidative stress, suppress neuroinflammatory responses, inhibit amyloid aggregation, attenuate tau pathology, and promote neuronal survival. Additionally, certain polysaccharides such as chitosan and alginate have demonstrated significant potential as nanocarriers for targeted drug delivery across the blood-brain barrier. This review summarizes recent advances in understanding the signaling pathways associated with AD and highlights the emerging therapeutic potential of marine-derived polysaccharides as multi-target neuroprotective agents. Overall, these marine biomolecules represent promising candidates for developing novel therapeutic strategies to mitigate neurodegeneration and improve cognitive function in Alzheimer's disease.

Nanogels (NGs) are versatile polymeric nanocarriers with high drug loading capacity and colloidal stability, making them pivotal candidates for targeted biomedical applications. Surface functionalization with biomolecules is essential for selective targeting therapies; however, conventional covalent conjugation can compromise the activity of sensitive ligands (e.g., proteins and antibodies). The His-tag strategy offers a reversible, oriented binding through coordination with transition metal ions, widely used in protein purification, but scarcely explored for polymeric NG decoration. Here, we developed polyallylamine-based NGs via an emulsion-evaporation process. The NG outer layer was functionalized with lysine-conjugated nitrilotriacetic acid to chelate Ni2+ or Co3+ ions, enabling the His-tag strategy. To validate this approach, a His-Rhodamine compound was used as a representative His-tag structure, mimicking potential bioactive ligands or motifs. Our results demonstrate that Co3+ provides superior His-tag grafting density compared to Ni2+, preserving the biocompatibility of the nanoscaffold. The cobalt-complexed NGs were also tested as cisplatin delivery systems, showing enhanced therapeutic performance compared with the administration of the free drug in ovarian cancer cells. Overall, the cobalt-mediated His-tag conjugation proved to be an efficient approach for the noncovalent surface decoration of polymeric NGs, defining a reliable alternative for the functionalization of this type of nanoscaffolds. Owing to the presence of His-tag functionalities in several biomolecules, the proposed strategy can be readily extended to a wide range of His-tag-based species, thus providing a flexible platform for the design of advanced, targeted NGs with improved selectivity and therapeutic potential.

Ribonuclease A (RNase A) is a clinically relevant biomarker whose aberrant activity compromises RNA stability and interferes with RNA-based therapeutics, highlighting the need for rapid and ultrasensitive detection tools. In this work, we developed a CRISPR/Cas12a-assisted biosensing platform integrated with a substrate-bridged magnetic bead-gold nanoparticle assembly (SB-MAC) for highly sensitive and selective RNase A detection. By optimizing AuNP loading density, RNA substrate/barcode DNA molar ratio, and enzymatic incubation conditions, the prepared dual-functionalized SB-MAC architecture enabled efficient substrate/RNase A cleavage interaction and significant signal amplification, yielding a limit of detection (LOD) of 0.16 pg mL-1 for RNase A. The sensor exhibited excellent specificity against structurally and functionally related biomolecules and demonstrated strong analytical performance when tested on serum and water samples, with recoveries obtained ranging from 104 to 110%. Owing to its modular substrate design and robust signal amplification, this DNA-assisted platform offers a versatile and clinically relevant tool for monitoring RNase A activity and can be readily adapted for detecting other nuclease-based biomarkers.

Extracellular vesicles (EVs) are nanoscale membrane-bound vesicles released by any cell type under both physiological and pathological conditions. They carry a wide array of bioactive molecules, including microRNAs (miRNAs), lipids, proteins and other small biomolecules, and therefore play a key role in intercellular communication by transferring functional cargo between cells. Plant-derived EVs (PDVs) are secreted by plant cells and, because of their natural abundance, PDVs are a compelling alternative to synthetic nanoparticles, particularly for drug delivery applications, due to their biocompatibility, low immunogenicity and intrinsic ability to encapsulate and transport therapeutic molecules. PDVs can enhance drug delivery by improving efficacy and safety, reducing dosage and toxicity, and enabling environmentally sustainable approaches. They also hold promises in diagnostics and nutraceuticals, where their immunomodulatory effects, disease-specific molecular signatures, and incorporation into functional foods may lead to significant health benefits. Despite these advances, challenges remain in standardizing PDVs isolation and characterization techniques and in ensuring reproducibility for clinical translation. Moreover, the transformative potential of PDVs to drive pharmaceutical and nutraceutical innovation and to promote sustainable healthcare solutions has also been underlined. This review provides a comprehensive analysis of PDVs, integrating research findings from 2014 to 2025 to summarize their sources, biochemical composition, isolation, characterization and numerous uses in the fields of biomedical and biotechnological research. Emphasis has been placed on the use of flow cytometry as an emerging, robust, and rapid technique for PDVs identification and characterization, underlining its relevance in clinical and nutraceutical applications.

While extracellular vesicles (EVs) are increasingly recognized for their diagnostic and therapeutic potential, many unknowns remain. An emerging and important concept in EV biology is the EV biomolecular corona, a dynamic layer of absorbed biomolecules to the EV membrane that influences EV behaviour, cellular uptake, biodistribution and function. In de-coronisation studies, a key challenge involves identifying effective purification methods to selectively and reliably remove enzymatically digested surface proteins. This study assesses the effectiveness of ultracentrifugation (UC) and ultrafiltration (UF) purification techniques following proteinase K (PK) treatment of pre-isolated natural killer cell-derived EVs (NK-EVs). The efficiency and specificity/selectivity of these purification methods in removing cleaved proteins while preserving EV physical properties (size), biomolecular profile (surface immunophenotyping, cytokine and proteomic profiling) and cytotoxicity against cancer cells were evaluated. While both methods achieve comparable NK-EV particle recovery, only UF purification selectively removed PK-cleaved proteins, as depicted in the protein-to-particle ratio, biomolecular profiling and NK-EV cytotoxicity after PK treatment. In contrast, UC purification caused non-specific corona disruption, dramatically reducing the cytokine payloads and abolishing NK-EV cytotoxicity. Interestingly, NTA and transmission electron microscopy (TEM) (positive staining) analyses showed that de-coronised EVs were smaller than their untreated counterpart. This finding suggests that PK treatment impacts surface-associated proteins with different sensitivity to proteolysis, an effect that remained consistent independent of the subsequent purification methods. Collectively, these results highlight UF as the purification method of choice for controlled de-coronisation studies, potentially supporting the advancements of EV research across multi-omics, investigatory, and preclinical applications.

The global incidence of cancer remains persistently high, with associated mortality rates remaining elevated owing to the challenges of early diagnosis and propensity for metastasis. The immunosuppressive "cold tumor" within the tumor microenvironment (TME), characterized by hypoxia, metabolic abnormalities, and immunosuppressive cellular infiltration, represents a key factor in treatment resistance and the failure of immunotherapies. Existing therapeutic approaches exhibit significant limitations that hinder curative outcomes. Tumor-derived exosomes (TEXs) frequently carry pro-cancer biomolecules, rendering single-exosome targeting strategies insufficient to reverse TME-mediated immunosuppression. Concurrently, danger signaling molecules released during immunogenic cell death (ICD) are readily neutralized by the immunosuppressive TME, resulting in inadequate and transient anti-tumor immune responses. Recent studies indicate that the TME, exosomes, and ICD do not function as isolated entities but rather constitute an interlinked signaling network. The TME modulates exosome biogenesis and release through hypoxic and inflammatory microenvironments while simultaneously attenuating the effects of ICD, thereby promoting immune evasion. Exosomes play a dual role in intercellular communication: TEXs amplify immunosuppressive signals, whereas engineered exosomes can deliver ICD inducers or immunomodulatory factors to reshape the immune state of the TME. ICD attempts to reverse TME suppression by releasing damage-associated molecular patterns (DAMPs); however, its effects require exosome-mediated long-range signal amplification and matrix penetration. Co-targeting the TME-exosome-ICD axis provides a mechanistic framework for enhancing the immunotherapy response by boosting DAMPs presentation, promoting antigen release, and facilitating immune cell infiltration. This approach also establishes a novel paradigm for reversing immunologically "cold" tumors towards an immunologically activated phenotype.

Recent advances in precision medicine and virotherapy have expanded the search for novel biomolecules with therapeutic potential. In this study, we employed a phage display-based platform to identify and characterize mimetic peptides of the Newcastle Disease Virus (NDV), a promising agent in oncolytic virotherapy and veterinary vaccinology. Following the immunization of gallus domesticus (White Leghorn) and the high-performance liquid chromatography (HPLC) purification of specific IgY antibodies, a Ph.D.-7™ phage library was screened against anti-NDV targets. We identified three high-affinity mimotopes (NDV-1, NDV-2, and NDV-3) that were further characterized through an integrated in silico workflow involving AlphaFold2 and PEP-FOLD3. Structural analysis revealed that NDV-3 exhibits a stable helical conformation, which correlates with its superior binding affinity observed in Phage-ELISA assays. Furthermore, B-cell epitope predictions (BepPred-3.0) highlighted the immunogenic potential of NDV-1. Our findings demonstrate a robust proof-of-concept for the identification of NDV-mimetic leads, providing a structural basis for the future development of targeted oncolytic strategies and next-generation avian vaccines. Further functional assays are required to validate the translational efficacy of these candidates in clinical and veterinary settings.

Phase separation (PS) has emerged as a fundamental biophysical process that organizes essential cellular processes through the formation of biomolecular condensates. These dynamic membrane-less assemblies reversibly form and dissolve in response to environmental and physiological stimuli, including changes in concentration, pH, temperature, or light. Such responsiveness makes biomolecular condensates highly attractive platforms for engineering applications, including drug delivery, biosensing, stimuli-responsive nanomedicine, and gene or protein transfection. Physiological cues induce phase separation that selectively partitions biomolecules into dense phases increasing the local concentrations leading to enhanced catalytic effects. This concentration-driven organization is particularly advantageous for enzymatic systems, where condensate formation has been shown to accelerate reaction kinetics by several fold. In this review we discuss how insights from cellular condensates are being translated into engineered systems, with emerging applications in biocatalysis, drug delivery, and related biomedical applications.