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On October 29, 2021, FDA granted accelerated approval to asciminib (Scemblix; Novartis), a tyrosine kinase inhibitor (TKI), for the treatment of adult patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more TKIs, and granted traditional approval to asciminib for adult patients with Ph+ CML in CP with the T315I mutation. The first indication was approved based on major molecular response (MMR) at 24 weeks in the ASCEMBL Study, a randomized trial comparing asciminib with bosutinib in patients who had failed two or more TKIs. This indication was ultimately granted traditional approval on October 12, 2022, based on safety data and MMR rate at 96 weeks of 38% (95% CI: 30, 46) in the asciminib arm vs. 16% (95% CI: 8, 26) in the bosutinib arm (p-value: 0.001). The second indication was approved based on MMR rate by 96 weeks of 49% (95% CI: 34, 64) in the single-arm CABL001X2101 Study. The most common (≥20%) adverse reactions included upper respiratory tract infections, musculoskeletal pain, headache, fatigue, nausea, rash, and diarrhea. The most common (≥20%) laboratory abnormalities were thrombocytopenia, neutropenia, anemia, lymphopenia, hypertriglyceridemia, hyperuricemia, increases in creatine kinase, ALT, AST, lipase, and amylase. This manuscript describes the basis for approval of these indications.
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Traditional camera-based single-molecule localization microscopy (SMLM), with its high imaging resolution and localization throughput, has made significant advancements in biological and chemical researches. However, due to the limitation of the fluorescence signal-to-noise ratio (SNR) of a single molecule, its resolution is difficult to reach to 5â nm. Optical lattice produces a nondiffracting beam pattern that holds the potential to enhance microscope performance through its high contrast and penetration depth. Here, we propose a new method named LatticeFLUX which utilizes the wide-field optical lattice pattern illumination for individual molecule excitation and localization. We calculated the Cramér-Rao lower bound of LatticeFLUX resolution and proved that our method can improve the single molecule localization precision by 2.4 times compared with the traditional SMLM. We propose a scheme using 9-frame localization, which solves the problem of uneven lattice light illumination. Based on the experimental single-molecule fluorescence SNR, we coded the image reconstruction software to further verify the resolution enhancement capability of LatticeFLUX on simulated punctate DNA origami, line pairs, and cytoskeleton. LatticeFLUX confirms the feasibility of using 2D structured light illumination to obtain high single-molecule localization precision under high localization throughput. It paves the way for further implementation of ultra-high resolution full 3D structured-light-illuminated SMLM.
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Visualizing the whole vascular network system is crucial for understanding the pathogenesis of specific diseases and devising targeted therapeutic interventions. Although the combination of light sheet microscopy and tissue-clearing methods has emerged as a promising approach for investigating the blood vascular network, leveraging the spatial resolution down to the capillary level and the ability to image centimeter-scale samples remains difficult. Especially, as the resolution improves, the issue of photobleaching outside the field of view poses a challenge to image the whole vascular network of adult mice at capillary resolution. Here, we devise a fluorescent microsphere vascular perfusion method to enable labeling of the whole vascular network in adult mice, which overcomes the photobleaching limit during the imaging of large samples. Moreover, by combining the utilization of a large-scale light-sheet microscope and tissue clearing protocols for whole-mouse samples, we achieve the capillary-level imaging resolution (3.2 × 3.2 × 6.5 µm) of the whole vascular network with dimensions of 45 × 15 × 82 mm in adult mice. This method thus holds great potential to deliver mesoscopic resolution images of various tissue organs for whole-animal imaging.
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Nanofluidic biosensors have been widely used for detection of analytes based on the change of system resistance before and after target-probe interactions. However, their sensitivity is limited when system resistance barely changes toward low-concentration targets. Here, we proposed a strategy to address this issue by means of target-induced change of local membrane potential under relatively unchanged system resistance. The local membrane potential originated from the directional diffusion of photogenerated carriers across nanofluidic biosensors and gated photoinduced ionic current signal before and after target-probe interactions. The sensitivity of such biosensors for the detection of biomolecules such as circulating tumor DNA (ctDNA) and lysozyme exceeds that of applying a traditional strategy by more than 3 orders of magnitude under unchanged system resistance. Such biosensors can specifically detect the small molecule biomarker in the blood sample between prostate cancer patients and healthy humans. The key advantages of such nanofluidic biosensors are therefore complementary to traditional nanofluidic biosensors, with potential applications in a point-of-care analytical tool.
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Técnicas Biosensibles , Masculino , Humanos , Transporte Iónico , ElectricidadRESUMEN
Nanopore sensing technology, as an emerging analytical method, has the advantages of simple operation, fast output, and label-free and has been widely used in fields such as protein analysis, gene sequencing, and biomarker detection. Inspired by biological ion channels, scientists have prepared various artificial solid-state nanopores/nanochannels. Biological ion channels have extremely high ion transport selectivity, while solid-state nanopores/nanochannels have poor selectivity. The selectivity of solid-state nanopores and nanochannels can be enhanced by modifying channel charge, varying pore size, incorporating specific chemical functionality, and adjusting operating (or solution) conditions. This Perspective highlights pore-in modification strategies for enhancing the selectivity of solid-state nanopore/nanochannel sensors by summarizing the articles published in the last 10 years. The future development prospects and challenges of pore-in modification in solid-state nanopore and nanochannel sensors are discussed. This Perspective helps readers better understand nanopore sensing technology, especially the importance of detection selectivity. We believe that solid-state nanopore/nanochannel sensors will soon enter our homes after various challenges.
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Nanoporos , Nanotecnología , Canales Iónicos , Transporte Iónico , TecnologíaRESUMEN
On May 25, 2022, FDA approved a supplemental application for ivosidenib (Tibsovo; Servier) extending the indication in patients with newly diagnosed IDH1-mutated acute myeloid leukemia (AML) in older adults or those with comorbidities to include the combination with azacitidine. The efficacy of ivosidenib in combination with azacitidine was evaluated in Study AG120-C-009, a phase 3, multicenter, double-blind, randomized (1:1), controlled study of ivosidenib or matched placebo in combination with azacitidine in adults with previously untreated AML with an IDH1 mutation who were 75 years or older or had comorbidities that precluded use of intensive induction chemotherapy. Efficacy was established on the basis of improved event-free survival and overall survival on the ivosidenib + azacitidine arm [HR, 0.35; 95% confidence interval (CI), 0.17-0.72; P = 0.0038, and HR, 0.44; 95% CI, 0.27-0.73; P = 0.0010], respectively. Furthermore, the rate and duration of complete remission (CR) were improved with ivosidenib versus placebo [CR 47% versus 15%, two-sided P < 0.0001; median duration of CR not estimable (NE; 95% CI, 13.0-NE) months versus 11.2 (95% CI, 3.2-NE) months. The safety profile of ivosidenib in combination with azacitidine was consistent with that of ivosidenib monotherapy, with important adverse reactions including differentiation syndrome (15%) and QT interval prolongation (20%).
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Azacitidina , Glicina/análogos & derivados , Leucemia Mieloide Aguda , Piridinas , Humanos , Anciano , Azacitidina/efectos adversos , Isocitrato Deshidrogenasa/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Mutación , Respuesta Patológica CompletaRESUMEN
The stoichiometry of molecular components within supramolecular biological complexes is often an important property to understand their biological functioning, particularly within their native environment. While there are well established methods to determine stoichiometryin vitro, it is presently challenging to precisely quantify this propertyin vivo,especially with single molecule resolution that is needed for the characterization stoichiometry heterogeneity. Previous work has shown that optical microscopy can provide some information to this end, but it can be challenging to obtain highly precise measurements at higher densities of fluorophores. Here we provide a simple approach using already established procedures in single-molecule localization microscopy (SMLM) to enable precise quantification of stoichiometry within individual complexes regardless of the density of fluorophores. We show that by focusing on the number of fluorophore detections accumulated during the quasi equilibrium-state of this process, this method yields a 50-fold improvement in precision over values obtained from images with higher densities of active fluorophores. Further, we show that our method yields more correct estimates of stoichiometry with nuclear pore complexes and is easily adaptable to quantify the DNA content with nanodomains of chromatin within individual chromosomes inside cells. Thus, we envision that this straightforward method may become a common approach by which SMLM can be routinely employed for the accurate quantification of subunit stoichiometry within individual complexes within cells.
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Microscopía , Imagen Individual de Molécula , Cromatina , Colorantes Fluorescentes , IonóforosRESUMEN
Introduction: Spermatogenesis is sustained by the homeostasis of self-renewal and differentiation of undifferentiated spermatogonia throughout life, which is regulated by transcriptional and posttranscriptional mechanisms. B cell-specific Moloney murine leukemia virus integration site 1 (BMI1), one of spermatogonial stem cell markers, is a member of Polycomb repressive complex 1 (PRC1) and important to spermatogenesis. However, the mechanistic underpinnings of how BMI1 regulates spermatogonia fate remain elusive. Methods: We knocked down BMI1 by siRNA to investigate the role of BMI1 in undifferentiated spermatogonia. Differentially expressed genes were identified by RNA-seq and used for KEGG pathway analysis. We performed ChIP-seq analysis in wild type and BMI1 knockdown cells to explore the underlying molecular mechanisms exerted by BMI1. BMI1-associated alterations in repressive histone modifications were detected via Western blotting and ChIP-seq. Furthermore, we performed mass spectrometry and Co-immunoprecipitation assays to investigate BMI1 co-factors. Finally, we demonstrated the genomic regions occupied by both BMI1 and its co-factor. Results: BMI1 is required for undifferentiated spermatogonia maintenance by both repressing and activating target genes. BMI1 preserves PI3K-Akt signaling pathway for spermatogonia proliferation. Decrease of BMI1 affects the deposition of repressive histone modifications H2AK119ub1 and H3K27me3. BMI also positively regulates H3K27ac deposited genes which are associated with proliferation. Moreover, we demonstrate that BMI1 interacts with Sal-like 4 (SALL4), the transcription factor critical for spermatogonia function, to co-regulate gene expression. Discussion: Overall, our study reveals that BMI1 safeguards undifferentiated spermatogonia fate through multi-functional roles in regulating gene expression programs of undifferentiated spermatogonia.
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The FDA granted accelerated approval for amivantamab-vmjw (hereafter referred to as amivantamab), a bispecific antibody directed against EGFR and mesenchymal-epithelial transition receptor, on May 21, 2021, for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. Approval was based on results of an ongoing, multicenter, nonrandomized, open-label, multicohort clinical trial (CHRYSALIS, NCT02609776), demonstrating a substantial overall response rate (ORR) and durable responses, with an ORR of 40% [95% confidence interval (CI): 29-51] and a median response duration of 11.1 months (95% CI: 6.9-not evaluable). Guardant360 CDx was contemporaneously approved as a companion diagnostic for this indication to identify EGFR exon 20 insertion mutations in plasma specimens. The most notable safety finding was the high incidence (66%) of infusion-related reactions, which is addressed in both the Dosage and Administration and Warnings and Precautions sections of the product label. Other common adverse reactions (occurring in ≥20% of patients) were rash, paronychia, musculoskeletal pain, dyspnea, nausea and vomiting, fatigue, edema, stomatitis, cough, and constipation. The approval of amivantamab was the first approval of a targeted therapy for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutagénesis Insercional , Receptores ErbB/genética , Exones , Mutación , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) can profile genome-wide epigenetic marks associated with regulatory genomic elements. However, conventional ChIP-seq is challenging when examining limited numbers of cells. Here, we developed a new technique by supplementing carrier materials of both chemically modified mimics with epigenetic marks and dUTP-containing DNA fragments during conventional ChIP procedures (hereafter referred to as 2cChIP-seq), thus dramatically improving immunoprecipitation efficiency and reducing DNA loss of low-input ChIP-seq samples. Using this strategy, we generated high-quality epigenomic profiles of histone modifications or DNA methylation in 10-1000 cells. By introducing Tn5 transposase-assisted fragmentation, 2cChIP-seq reliably captured genomic regions with histone modification at the single-cell level in about 100 cells. Moreover, we characterized the methylome of 100 differentiated female germline stem cells (FGSCs) and observed a particular DNA methylation signature potentially involved in the differentiation of mouse germline stem cells. Hence, we provided a reliable and robust epigenomic profiling approach for small cell numbers and single cells.
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ADN , Epigenómica , Ratones , Animales , Epigenómica/métodos , Análisis de Secuencia de ADN/métodos , ADN/química , Metilación de ADN , Recuento de CélulasRESUMEN
Aim: Molecular alterations in drug targets may result in differential drug activity. Therefore, the authors aimed to characterize how molecular alterations in drug targets were assessed during drug development. Materials & methods: The authors analyzed nonclinical and clinical study reports submitted to the US FDA for novel drugs approved in 2020 to determine if in vitro studies, animal models or clinical studies assessed molecular alterations in the drug target. Results & conclusion: Assessment of the impact of molecular alterations in drug targets on drug activity varies considerably depending on the type of assessment and therapeutic area. Premarket assessment of drug target molecular alterations is common in the oncology setting, less frequent in the genetic disease setting and rare for other diseases.
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Aprobación de Drogas , Sistemas de Liberación de Medicamentos , Aprobación de Drogas/métodos , Humanos , Proyectos de Investigación , Estados Unidos , United States Food and Drug AdministrationRESUMEN
The folding of interphase chromatin into highly compact mitotic chromosomes is one of the most recognizable changes during the cell cycle. However, the structural organization underlying this drastic compaction remains elusive. Here, we combine several super resolution methods, including structured illumination microscopy (SIM), binding-activated localization microscopy (BALM), and atomic force microscopy (AFM), to examine the structural details of the DNA within the mitotic chromosome, both in the native state and after up to 30-fold extension using single-molecule micromanipulation. Images of native chromosomes reveal widespread â¼125 nm compact granules (CGs) throughout the metaphase chromosome. However, at maximal extensions, we find exclusively â¼90 nm domains (mitotic nanodomains, MNDs) that are unexpectedly resistant to extensive forces of tens of nanonewtons. The DNA content of the MNDs is estimated to be predominantly â¼80 kb, which is comparable to the size of the inner loops predicted by a recent nested loop model of the mitotic chromosome. With this DNA content, the total volume expected of the human genome assuming closely packed MNDs is nearly identical to what is observed. Thus, altogether, these results suggest that these mechanically stable MNDs, and their higher-order assembly into CGs, are the dominant higher-level structures that underlie the compaction of chromatin from interphase to metaphase.
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Cromatina , Cromosomas , Humanos , Cromosomas/metabolismo , Metafase , ADN/metabolismo , MicromanipulaciónRESUMEN
There is presently intense interest in the development of synthetic nanopores that recapitulate the functional properties of biological water channels for a wide range of applications. To date, all known synthetic water channels have a hydrophobic lumen, and while many exhibit a comparable rate of water transport as biological water channels, there is presently no rationally designed system with the ability to regulate water transport, a critical property of many natural water channels. Here, we describe a self-assembling nanopore consisting of stacked macrocyclic molecules with a hybrid hydrophilic/hydrophobic lumen exhibiting water transport that can be regulated by alkali metal ions. Stopped-flow kinetic assays reveal a non-monotonic-dependence of transport on cation size as well as a strikingly broad range of water flow, from essentially none in the presence of the sodium ion to as high a flow as that of the biological water channel, aquaporin 1, in the absence of the cations. All-atom molecular dynamics simulations show that the mechanism underlying the observed sensitivity is the binding of cations to defined sites within this hybrid pore, which perturbs water flow through the channel. Thus, beyond revealing insights into factors that can modulate a high-flux water transport through sub-nm pores, the obtained results provide a proof-of-concept for the rational design of next-generation, controllable synthetic water channels.
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Alternative polyadenylation (APA) is an important RNA post-transcriptional process, which can generate diverse mRNA isoforms. Increasing evidence shows that APA is involved in cell self-renewal, development, immunity, and cancer. CPSF6 is one of the core proteins of CFIm complex and can modulate the APA process. Although it has been reported to play oncogenic roles in cancer, the underlying mechanisms remain unclear. The aim of the present study was to characterize CPSF6 in human gastric cancer (GC). We observed that CPSF6 was upregulated in GC. Knockdown of CPSF6 inhibited proliferation and enhanced apoptosis of GC cells both in vitro and in vivo. Global APA site profiling analysis revealed that knockdown of CPSF6 induced widespread 3'UTR shortening of genes in GC cells, including VHL. We also found CPSF6 negatively regulated the expression of VHL through APA and VHL short-3'UTR isoform enhanced apoptosis and inhibited cell growth in GC cells. Our data suggested that CPSF6-induced cell proliferation and inhibition of apoptosis were mediated by the preferential usage of poly(A) in VHL. Our data provide insights into the function of CPSF6 and may imply potential therapeutic targets against GC.
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The FDA granted accelerated approval for pralsetinib on September 4, 2020 for non-small cell lung cancer (NSCLC) and December 1, 2020 for thyroid cancer, for: (i) adult patients with metastatic RET fusion-positive NSCLC, (ii) adult and pediatric patients ≥12 years of age with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy, and (iii) adult and pediatric patients ≥12 years of age with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine refractory (if radioactive iodine is appropriate). Approval was based on the results of a multicenter, open-label, multi-cohort clinical trial (ARROW, NCT03037385), demonstrating substantial overall response rates (ORR) and durable responses in patients with RET-altered tumors. ORRs within the approved patient populations ranged from 57% [95% confidence interval (CI), 46-68] in patients with RET fusion-positive NSCLC previously treated with platinum chemotherapy to 89% (95% CI, 52-100) in patients with RET fusion-positive thyroid cancer, with response duration of at least 6 months in most responders. The product label includes warnings and precautions for pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, tumor lysis syndrome, risk of impaired wound healing, and embryo-fetal toxicity. This article summarizes the major considerations during FDA review leading to the approval of pralsetinib.
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Antineoplásicos/uso terapéutico , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/genética , Aprobación de Drogas , Fusión Génica , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Proteínas Proto-Oncogénicas c-ret/genética , Pirazoles/uso terapéutico , Piridinas/uso terapéutico , Pirimidinas/uso terapéutico , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genética , Humanos , Estados UnidosRESUMEN
Optical imaging has played a vital role in development of biomedicine and image-guided theragnostic. Nevertheless, the clinical translation of optical molecular imaging for deep-tissue visualization is still limited by poor signal-to-background ratio and low penetration depth owing to light scattering and tissue autofluorescence. Hence, to facilitate precise diagnosis and accurate surgery excision in clinical practices, the responsive optical probes (ROPs) are broadly designed for specific reaction with biological analytes or disease biomarkers via chemical/physical interactions for photoacoustic and second near-infrared fluorescence (NIR-II, 900-1700 nm) fluorescence imaging. Herein, the recent advances in the development of ROPs including molecular design principles, activated mechanisms and treatment responses for photoacoustic and NIR-II fluorescence imaging are reviewed. Furthermore, the present challenges and future perspectives of ROPs for deep-tissue imaging are also discussed.
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Fluorescencia , Colorantes Fluorescentes/química , Neoplasias/diagnóstico por imagen , Imagen Óptica , Técnicas Fotoacústicas , Humanos , Rayos InfrarrojosRESUMEN
BACKGROUND: Alternative polyadenylation (APA) is an important mechanism of gene expression regulation through generation of RNA isoforms with distinct 3' termini. Increasing evidence has revealed that APA is actively involved in development and disease, including hepatocellular carcinoma (HCC). However, how APA functions in tumor formation and progression remains elusive. In this study, we investigated the role of cleavage factor I (CFIm) subunit CPSF6 in human hepatocellular carcinoma (HCC). METHODS: Expression levels of CPSF6 in clinical tissues and cell lines were determined by qRT-PCR and western blot. Functional assays, including the cell number, MTT, colony formation and transwell, were used to determine the oncogenic role of CPSF6 in HCC. Animal experiments were used to determine the role of CPSF6 in HCC tumorigenicity in vivo. Deep sequencing-based 3 T-seq was used to profile the transcriptome-wide APA sites in both HCC cells and CPSF6 knockdown HCC cells. The function of CPSF6-affected target NQO1 with distinct 3'UTRs was characterized by metabolism assays. RESULTS: We observed CPSF6 was upregulated in HCC and the high expression of CPSF6 was associated with poor prognosis in patients. Overexpression of CPSF6 promoted proliferation, migration and invasion of HCC cells in vitro and in vivo. Transcriptome-wide APA profiling analysis indicated that high expression of CPSF6 promoted the favorable usage of the proximal poly(A) site in the 3'UTR of NQO1. We demonstrated CPSF6-induced tumorigenic activities were mediated by the NQO1 isoform with short 3'UTR. Furthermore, we found that CPSF6 induced metabolic alterations in liver cells through NQO1. CONCLUSION: CPSF6 plays a critical role in HCC progression by upregulating NQO1 expression through APA. These findings provide evidence to demonstrate that APA of NQO1 contributes to HCC progression and may have implications for developing new therapeutic strategy against this disease.
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Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Factores de Escisión y Poliadenilación de ARNm/metabolismo , Animales , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Células Hep G2 , Xenoinjertos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Masculino , Ratones , Ratones Desnudos , NAD(P)H Deshidrogenasa (Quinona)/genética , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Poliadenilación , Análisis de Supervivencia , Regulación hacia Arriba , Factores de Escisión y Poliadenilación de ARNm/genéticaRESUMEN
Genetic heterogeneity of tumor is closely related to its clonal evolution, phenotypic diversity and treatment resistance, and such heterogeneity has only been characterized at single-cell sub-chromosomal scale in liver cancer. Here we reconstructed the single-variant resolution clonal evolution in human liver cancer based on single-cell mutational profiles. The results indicated that key genetic events occurred early during tumorigenesis, and an early metastasis followed by independent evolution was observed in primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. By parallel single-cell RNA-Seq, the transcriptomic phenotype of HCC was found to be related with genetic heterogeneity. For the first time we reconstructed the single-cell and single-variant clonal evolution in human liver cancer, and dissection of both genetic and phenotypic heterogeneity will facilitate better understanding of their relationship.
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Carcinoma Hepatocelular/genética , Evolución Clonal , Neoplasias Hepáticas/genética , Humanos , Mutación , Análisis de la Célula Individual , Células Tumorales CultivadasRESUMEN
Materials that can regulate the composition and structure of the cell membrane to fabricate engineered cells with defined functions are in high demand. Compared with other biomolecules, DNA has unique advantages in cell membrane engineering due to its excellent programmability and biocompatibility. Especially, the near-atomic scale precision of DNA nanostructures facilitates the investigation of structure-property relations on the cell membrane. In this review, first the state of the art of functional DNA nanostructures is summarized, and then the overview of the use of DNA nanostructures to engineer the cell membrane is presented. Subsequently, applications of DNA nanostructures in modifying cell membrane morphology, controlling ions transport, and synthesizing high precise liposomes are highlighted. Finally, the challenges and outlook on using DNA nanostructures for cell membrane engineering are discussed.