bims-novged Biomed News
on Non-viral vectors for gene delivery
Issue of 2021‒08‒01
thirteen papers selected by
Benjamin Winkeljann
Ludwig-Maximilians University
  1. One-Component Multifunctional Sequence-Defined Ionizable Amphiphilic Janus Dendrimer Delivery Systems for mRNA.
  2. Antibody-siRNA conjugates (ARCs) using multifunctional peptide as a tumor enzyme cleavable linker mediated effective intracellular delivery of siRNA.
  3. Size-Dependent Drug Loading, Gene Complexation, Cell Uptake, and Transfection of a Novel Dendron-Lipid Nanoparticle for Drug/Gene Co-delivery.
  4. A novel method for the development of plasmid DNA-loaded nanoliposomes for cancer gene therapy.
  5. A core-shell nanoplatform as a nonviral vector for targeted delivery of genes to the retina.
  6. Nanomedicine-based combination of dexamethasone palmitate and MCL-1 siRNA for synergistic therapeutic efficacy against rheumatoid arthritis.
  7. Lactate Consumption via Cascaded Enzymes Combined VEGF siRNA for Synergistic Anti-Proliferation and Anti-Angiogenesis Therapy of Tumors.
  8. Therapeutic inhibitory RNA in head and neck cancer via functional targeted lipid nanoparticles.
  9. Gene-editing by CRISPR-Cas9 in combination with anthracycline therapy via tumor microenvironment-switchable, EGFR-targeted, and nucleus-directed nanoparticles for head and neck cancer suppression.
  10. Impact of molecular rigidity on the gene delivery efficiency of core-shell tecto dendrimers.
  11. PEGylation of Guanidinium and Indole Bearing Poly(methacrylamide)s - Biocompatible Terpolymers for pDNA Delivery.
  12. Polymeric nanoparticle mediated inhibition of miR-21 with enhanced miR-124 expression for combinatorial glioblastoma therapy.
  13. Stable Retinoid Analogue Targeted Dual pH-Sensitive Smart Lipid ECO/pDNA Nanoparticles for Specific Gene Delivery in the Retinal Pigment Epithelium.
  1. J Am Chem Soc. 2021 Jul 29.
    One-Component Multifunctional Sequence-Defined Ionizable Amphiphilic Janus Dendrimer Delivery Systems for mRNA.
    Dapeng Zhang, Elena N Atochina-Vasserman, Devendra S Maurya, Ning Huang, Qi Xiao, Nathan Ona, Matthew Liu, Hamna Shahnawaz, Houping Ni, Kyunghee Kim, Margaret M Billingsley, Darrin J Pochan, Michael J Mitchell, Drew Weissman, Virgil Percec.
      Efficient viral or nonviral delivery of nucleic acids is the key step of genetic nanomedicine. Both viral and synthetic vectors have been successfully employed for genetic delivery with recent examples being DNA, adenoviral, and mRNA-based Covid-19 vaccines. Viral vectors can be target specific and very efficient but can also mediate severe immune response, cell toxicity, and mutations. Four-component lipid nanoparticles (LNPs) containing ionizable lipids, phospholipids, cholesterol for mechanical properties, and PEG-conjugated lipid for stability represent the current leading nonviral vectors for mRNA. However, the segregation of the neutral ionizable lipid as droplets in the core of the LNP, the "PEG dilemma", and the stability at only very low temperatures limit their efficiency. Here, we report the development of a one-component multifunctional ionizable amphiphilic Janus dendrimer (IAJD) delivery system for mRNA that exhibits high activity at a low concentration of ionizable amines organized in a sequence-defined arrangement. Six libraries containing 54 sequence-defined IAJDs were synthesized by an accelerated modular-orthogonal methodology and coassembled with mRNA into dendrimersome nanoparticles (DNPs) by a simple injection method rather than by the complex microfluidic technology often used for LNPs. Forty four (81%) showed activity in vitro and 31 (57%) in vivo. Some, exhibiting organ specificity, are stable at 5 °C and demonstrated higher transfection efficiency than positive control experiments in vitro and in vivo. Aside from practical applications, this proof of concept will help elucidate the mechanisms of packaging and release of mRNA from DNPs as a function of ionizable amine concentration, their sequence, and constitutional isomerism of IAJDs.
    DOI:  https://doi.org/10.1021/jacs.1c05813
  2. Int J Pharm. 2021 Jul 23. pii: S0378-5173(21)00746-8. [Epub ahead of print] 120940
    Antibody-siRNA conjugates (ARCs) using multifunctional peptide as a tumor enzyme cleavable linker mediated effective intracellular delivery of siRNA.
    Zhili Yu, Xiaojuan Zhang, Xing Pei, Weiran Cao, Junxiao Ye, Jianxin Wang, Lu Sun, Fei Yu, Jiancheng Wang, Nan Li, Kyuri Lee, Stefan Barth, Victor C Yang, Huining He.
      The tissue-specific targeted delivery and efficient cellular uptake of siRNAs are the main obstacles to their clinical application. Antibody-siRNA-conjugates (ARCs) can deliver siRNA by exploiting the targeting property of antibodies like antibody-drug conjugates (ADCs). However, the effective conjugation of antibodies and siRNAs and the release of siRNAs specifically at target sites have posed challenges to the development of ARCs. In this study, the successful conjugation of antibodies and siRNAs was achieved using a multifunctional peptide as a linker, composed of a cell-penetrating peptide (CPP) and a substrate peptide (SP), which is highly expressed in solid tumors. The resulting antibody-multifunctional peptide (SP-CPP)-siRNA system delivered the siRNA to target tumor cells by the specific binding of the antibody. Once the enzymes on the tumor cell surface hydrolyzed the substrate peptide linker, siRNA-CPP was released from ARCs. The released siRNA-CPP entered the targeted cells via the cellular penetrating ability of CPP, resulting in improved siRNA-mediated gene silencing efficiency, verified both in vitro and in vivo. After intravenous administration, the designed ARCs achieved approximately 66.7% EGFP (Enhanced Green Fluorescent Protein) downregulation efficiency in nude mice xenografted with the HCT116-EGFP tumor model. The proposed system provides a prospective choice for ARC production and the safe and efficient delivery of siRNAs.
    Keywords:  antibody; cell penetrating peptide; enzyme activatable; low molecular weight protamine; siRNA delivery
    DOI:  https://doi.org/10.1016/j.ijpharm.2021.120940
  3. Biomacromolecules. 2021 Jul 28.
    Size-Dependent Drug Loading, Gene Complexation, Cell Uptake, and Transfection of a Novel Dendron-Lipid Nanoparticle for Drug/Gene Co-delivery.
    Ashita Nair, Jiyoon Bu, Jason Bugno, Piper A Rawding, Luke J Kubiatowicz, Woo-Jin Jeong, Seungpyo Hong.
      Dendron micelles have shown promising results as a multifunctional delivery system, owing to their unique molecular architecture. Herein, we have prepared a novel poly(amidoamine) (PAMAM) dendron-lipid hybrid nanoparticle (DLNP) as a nanocarrier for drug/gene co-delivery and examined how the dendron generation of DLNPs impacts their cargo-carrying capabilities. DLNPs, formed by a thin-layer hydration method, were internally loaded with chemo-drugs and externally complexed with plasmids. Compared to generation 2 dendron DLNP (D2LNPs), D3LNPs demonstrated a higher drug encapsulation efficiency (31% vs 87%) and better gene complexation (minimal N/P ratio of 20:1 vs 5:1 for complexation) due to their smaller micellar aggregation number and higher charge density, respectively. Furthermore, D3LNPs were able to avoid endocytosis and subsequent lysosomal degradation and demonstrated a higher cellular uptake than D2LNPs. As a result, D3LNPs exhibited significantly enhanced antitumor and gene transfection efficacy in comparison to D2LNPs. These findings provide design cues for engineering multifunctional dendron-based nanotherapeutic systems for effective combination cancer treatment.
    DOI:  https://doi.org/10.1021/acs.biomac.1c00541
  4. Drug Deliv Transl Res. 2021 Jul 28.
    A novel method for the development of plasmid DNA-loaded nanoliposomes for cancer gene therapy.
    Behzad Baradaran, Ali Mohammadi, Sara Shamekhi, Nikoo Majidazar, Azita Dilmaghani, Saiedeh Razi Soofiyani, Nigel Aj McMillan, Farzaneh Lotfipour, Somayeh Hallaj-Nezhadi.
      We aimed to develop a simple yet novel method to prepare plasmid DNA-loaded nanoliposomes for cancer gene therapy. Murine interleukin-12 (mIL-12) pDNA-loaded nanoliposomes were prepared via novel freeze-drying of a monophase solution method. The physicochemical characteristics, cytotoxicity, and transfection efficiency of the prepared nanoliposomes in murine CT-26 colon carcinoma cells were evaluated. Furthermore, tumor progression and survival rate in CT-26 colon carcinoma-bearing BALB/c mice subsequent to direct intratumoral injections were investigated over a period of 40 days. Using this preparation method, nanoliposomes with particle size of around 300 nm and zeta potential of 96.5 mV were obtained. The transmission electron microscope results showed that the liposomes were nano-sized and almost spherical. The agarose gel retardation assay revealed the pDNA encapsulation in the nanoliposomes. The nanoliposomes with 72.4% encapsulation efficiency and low cell toxicity could significantly improve mIL-12 expression by approximately 25-fold relative to the naked mIL-12 pDNA. There was a significant tumor growth inhibition after repeated injections of mIL-12 pDNA-loaded nanoliposomes. This is the first study on the freeze-drying of a monophase solution method as a simple yet novel technique for the preparation of pDNA-loaded nanoliposomes. Given the ease of preparation method and promising in vitro and in vivo characteristics, this investigation demonstrates advances in pDNA lipid formulation for cancer gene therapy.
    Keywords:  Cancer; Gene therapy; IL-12; Nanoliposome; Plasmid DNA
    DOI:  https://doi.org/10.1007/s13346-021-01034-0
  5. Acta Biomater. 2021 Jul 27. pii: S1742-7061(21)00491-8. [Epub ahead of print]
    A core-shell nanoplatform as a nonviral vector for targeted delivery of genes to the retina.
    Guoxin Tan, Dandan Liu, Renfang Zhu, Hao Pan, Jiayang Li, Weisan Pan.
      Retinal diseases, including age-related macular degeneration (AMD), are a major cause of blindness. Efficient delivery of therapeutic genes to retinal cells to treat retinal disease is a formidable challenge. In this study, we developed a core-shell nanoplatform composed of a core and two external layers for targeted delivery of the gene to the retina. The inner core was composed of amino acid-functionalized dendrimers and a nuclear localization signal (NLS) for DNA complexation, nuclear transport and efficient transfection. The inner core was coated in a lipid bilayer that comprised pH-sensitive lipids as the inner shell layer. Hyaluronic acid (HA)-1,2-dioleoylphosphatidylethanolamine (DOPE) as the outermost shell layer was used for retinal cell targeting. This core-shell nanoplatform was developed so that the mobility in the vitreous body of these negatively charged carriers would not be affected by their surface charge, allowing diffusion into the retina, uptake into the retinal cells via CD44-mediated internalization, and finally transport into the nucleus by the NLS. The designed nanoparticles showed safety both in vitro and in vivo and inhibited the expression of VEGF under hypoxia-mimicking conditions. In vitro angiogenesis assays exhibited significant inhibitory effects on cell migration and tube formation. The in vivo assays indicated that this nanoplatform could be delivered to the retina. Taken together, this nanoplatform has the potential to transfer gene material into the retina for the treatment of retinal diseases, including AMD.
    Keywords:  angiogenesis; gene delivery; nonviral vectors; nuclear localization signal; retina
    DOI:  https://doi.org/10.1016/j.actbio.2021.07.053
  6. Drug Deliv Transl Res. 2021 Jul 30.
    Nanomedicine-based combination of dexamethasone palmitate and MCL-1 siRNA for synergistic therapeutic efficacy against rheumatoid arthritis.
    Yanmei Li, Shitong Wei, Yonghua Sun, Shihua Zong, Yameng Sui.
      The main aim of this research was to design a MCL-1 siRNA and dexamethasone (DEX)-loaded folate modified poly(lactide-co-glycolide) (PLGA)-based polymeric micelles with an eventual goal to improve the therapeutic outcome in the rheumatoid arthritis (RA). Polymeric micelles encapsulating the MCL-1 siRNA and DEX was successfully developed and observed to be stable. Physicochemical characteristics such as particle size and particle morphology were ideal for the systemic administration. Folate-conjugated DEX/siRNA-loaded polymeric micelles (DS-FPM) significantly lowered the MCL-1 mRNA expression compared to either DEX/siRNA-loaded polymeric micelles (DS-PM) or free siRNA in Raw264.7 cells and macrophage cells suggesting the importance of targeted nanocarriers. Most importantly, DS-FPM exhibited a greatest decrease in the hind paw volume with lowest clinical score compared to any other treated group indicating a superior anti-inflammatory activity. DS-FPM showed significantly lower levels of the TNF-α and IL-1β compared to AIA model and free groups. The folate receptor (FR)-targeting property of DS-FPM has been demonstrated to be a promising delivery platform for the effective delivery of combination therapeutics (siRNA and DEX) toward the treatment of rheumatoid arthritis.
    Keywords:  Dexamethasone; Folate receptors; Inflammation; Polymer micelles; Rheumatoid arthritis; siRNA
    DOI:  https://doi.org/10.1007/s13346-021-01037-x
  7. Adv Healthc Mater. 2021 Jul 26. e2100799
    Lactate Consumption via Cascaded Enzymes Combined VEGF siRNA for Synergistic Anti-Proliferation and Anti-Angiogenesis Therapy of Tumors.
    Yan Tang, Changhao Jia, Yu Wang, Wenjun Wan, Hui Li, Gui Huang, Xuenong Zhang.
      Lactate, as the most abundant component with concentrations of 4-40 mm in tumors, contributes to the regulation of metabolic pathways, angiogenesis, and immunosuppression, exhibiting remarkable potential in cancer treatment. Therefore, a codelivery strategy that combined the cascaded enzymes Lactate oxidase/Catalase (LOx/CAT) and vascular endothelial growth factor (VEGF) siRNA (siVEGF) to suppress tumor proliferation and angiogenesis synergistically is creatively proposed. In brief, the cationic liposomes (LIP) encapsulated with LOx/CAT and siVEGF via hydrophilic interaction and electrostatic adsorption followed by coating with PEGylated phenylboronic acid (PP) is established (PPL@[LOX+CAT]). Moreover, a simple 3-aminophenylboronic acid (PBA)-shielded strategy via fructose (Fru) is applied to further enhance the targeting efficiency in the tumor site. The obtained co-encapsulated nanoparticles (NPs) can simultaneous intracellular release of LOx/CAT and siVEGF, and the collaborative use of LOx and CAT can promote lactate consumption even under a hypoxic tumor microenvironment (TME) without producing systemic toxicity. The combined application of lactate depletion and VEGF silencing demonstrated the efficient migration suppression of 4T1 cells in vitro and superior antitumor and antimetastatic properties in vivo. This work offers a promising tumor treatment strategy via integrating cascaded enzymes and gene therapy, and explores a promising therapy regimen for 4T1 triple-negative breast cancer.
    Keywords:  antiangiogenesis; antiproliferation; cascaded dual-enzyme systems; combined therapy; lactate consumption; siVEGF
    DOI:  https://doi.org/10.1002/adhm.202100799
  8. J Control Release. 2021 Jul 22. pii: S0168-3659(21)00377-1. [Epub ahead of print]
    Therapeutic inhibitory RNA in head and neck cancer via functional targeted lipid nanoparticles.
    Liyona Kampel, Meir Goldsmith, Srinivas Ramishetti, Nuphar Veiga, Daniel Rosenblum, Anna Gutkin, Sushmita Chatterjee, Moran Penn, Galya Lerman, Dan Peer, Nidal Muhanna.
      Currently there are no specific therapies addressing the distinctive biology of human papillomavirus (HPV)-induced cancer approved for clinical use. Short interfering RNA (siRNA) has much potential for therapeutic manipulation of HPV E6/E7 oncoproteins. Lipid-based nanoparticles (LNPs) can be utilized for systemic transportation and delivery of siRNA at target site. We recently developed a recombinant protein linker that enables uniform conjugation of targeting antibodies to the LNPs. Herein, we demonstrate the therapeutic efficacy of anti-E6/E7 siRNA delivered via targeted LNPs (tLNPs) in a xenograft HPV-positive tumor model. We show that anti-epidermal growth factor receptor (EGFR) antibodies, anchored to the LNPs as targeting moieties, facilitate cargo delivery but also mediate anti-tumor activity. Treatment with siE6 via tLNPs resulted in 50% greater reduction of tumor volume compared to treatment with siControl encapsulated in isoLNPs (coated with isotype control antibodies). We demonstrate superior suppression of HPV oncogenes and higher induction of apoptosis by the tLNPs both in vitro and in vivo. Altogether, the coupling of inhibitory siE6 with anti-EGFR antibodies, that further elicited anti-tumor effects, successfully restricted tumor progression. This system that combines potent siRNA and therapeutically functional tLNPs can be modulated against various cancer models.
    Keywords:  HPV; Head and neck cancer; Lipid-based nanoparticle; Targeting; siRNA
    DOI:  https://doi.org/10.1016/j.jconrel.2021.07.034
  9. Nanoscale Horiz. 2021 Jul 29.
    Gene-editing by CRISPR-Cas9 in combination with anthracycline therapy via tumor microenvironment-switchable, EGFR-targeted, and nucleus-directed nanoparticles for head and neck cancer suppression.
    Chen-Shen Wang, Chih-Hsien Chang, Tsai-Yu Tzeng, Anya Maan-Yuh Lin, Yu-Li Lo.
      Head and neck cancer (HNC) has a high incidence and a poor prognosis. Epirubicin, a topoisomerase inhibitor, is a potential anthracycline chemotherapeutic for HNC treatment. HuR (ELAVL1), an RNA-binding protein, plays a critical role in promoting tumor survival, invasion, and resistance. HuR knockout via CRISPR/Cas9 (HuR CRISPR) is a possible strategy for the simultaneous modulation of the various pathways of tumor progression. Multifunctional nanoparticles modified with pH-sensitive epidermal growth factor receptor (EGFR)-targeting and nucleus-directed peptides were designed for the efficient delivery of HuR CRISPR and epirubicin to human tongue squamous carcinoma SAS cells and SAS tumor-bearing mice. The pH-sensitive nanoparticles responded to the acidic pH value as a switch to expose the targeting peptides. The cellular uptake and transfection efficiency of these nanoparticles in SAS cells increased via EGFR targeting, ligand-mediated endocytosis, and endosomal escape. These nanoparticles showed low cytotoxicity towards normal oral keratinocyte NOK cells. CRISPR/Cas9 was transported into the nucleus via the nuclear directing peptide and successfully knocked out HuR to suppress proliferation, metastasis, and resistance in SAS cells. The multiple inhibition of EGFR/β-catenin/epithelial-mesenchymal transition pathways was mediated through modulating the EGFR/PI3K/mTOR/AKT axis. The co-treatment of epirubicin and HuR CRISPR in SAS cells further facilitated apoptosis/necroptosis/autophagy and caused cancer cell death. In combination with HuR CRISPR nanoparticles, the efficacy and safety of epirubicin nanoparticles against cancer in SAS tumor-bearing mice improved significantly. Collectively, these nanoparticles showed a tumor pH response, active EGFR targeting, and nuclear localization and thus offered a combinatorial spatiotemporal platform for chemotherapy and the CRISPR/Cas gene-editing system.
    DOI:  https://doi.org/10.1039/d1nh00254f
  10. J Mater Chem B. 2021 Jul 30.
    Impact of molecular rigidity on the gene delivery efficiency of core-shell tecto dendrimers.
    Dayuan Wang, Liang Chen, Yue Gao, Cong Song, Zhijun Ouyang, Changsheng Li, Serge Mignani, Jean-Pierre Majoral, Xiangyang Shi, Mingwu Shen.
      We report the construction of two types of core-shell tecto dendrimers (CSTDs) with different core rigidities to illustrate the impact of molecular rigidity on their gene delivery efficiency. Our study reveals that CSTDs designed with rigid cores enable promoted gene delivery, providing many possibilities for a wide range of gene delivery-associated biomedical applications.
    DOI:  https://doi.org/10.1039/d1tb01328a
  11. Macromol Biosci. 2021 Jul 26. e2100146
    PEGylation of Guanidinium and Indole Bearing Poly(methacrylamide)s - Biocompatible Terpolymers for pDNA Delivery.
    Ceren Cokca, Franz J Hack, Daniel Costabel, Kira Herwig, Juliana Hülsmann, Patrick Then, Rainer Heintzmann, Dagmar Fischer, Kalina Peneva.
      This study describes the first example for shielding of a high performing terpolymer that consists of N-(2-hydroxypropyl)methacrylamide (HPMA), N-(3-guanidinopropyl)methacrylamide (GPMA), and N-(2-indolethyl)methacrylamide monomers (IEMA) by block copolymerization of a polyethylene glycol derivative - poly(nona(ethylene glycol)methyl ether methacrylate) (P(MEO9 MA)) via reversible addition-fragmentation chain transfer (RAFT) polymerization. The molecular weight of P(MEO9 MA) is varied from 3 to 40 kg mol-1 while the comonomer content of HPMA, GPMA, and IEMA is kept comparable. The influence of P(MEO9 MA) block with various molecular weights is investigated over cytotoxicity, plasmid DNA (pDNA) binding, and transfection efficiency of the resulting polyplexes. Overall, the increase in molecular weight of P(MEO9 MA) block demonstrates excellent biocompatibility with higher cell viability in L-929 cells and an efficient binding to pDNA at N/P ratio of 2. The significant transfection efficiency in CHO-K1 cells at N/P ratio 20 is obtained for block copolymers with molecular weight of P(MEO9 MA) up to 10 kg mol-1 . Moreover, a fluorescently labeled analogue of P(MEO9 MA), bearing perylene monoimide methacrylamide (PMIM), is introduced as a comonomer in RAFT polymerization. Polyplexes consisting of labeled block copolymer with 20 kg mol-1 of P(MEO9 MA) and pDNA are incubated in Hela cells and investigated through structured illumination microscopy (SIM).
    Keywords:  gene delivery; guanidinium; indole; methacrylamides; poly(ethylene glycol) methacrylate
    DOI:  https://doi.org/10.1002/mabi.202100146
  12. Biomaterials. 2021 Jul 20. pii: S0142-9612(21)00392-6. [Epub ahead of print]276 121036
    Polymeric nanoparticle mediated inhibition of miR-21 with enhanced miR-124 expression for combinatorial glioblastoma therapy.
    Yuanyuan Liu, Meng Zheng, Mingzhu Jiao, Chengnan Yan, Sen Xu, Qiuli Du, Marco Morsch, Jinlong Yin, Bingyang Shi.
      Glioblastoma (GBM) is the most common and fatal form of malignant brain tumor. Despite intensive effort, there is still no effective GBM treatment. Therefore, novel and more effective GBM therapeutic approaches are highly desired. In this study, we combined polymeric nanotechnology with microRNA (miRNA) regulation technology to develop a targeted polymeric nanoparticle to co-deliver anti-miR-21 and miR-124 into the brain to effectively treat GBM. The polymeric nanoparticle decorated with Angiopep-2 peptide not only can encapsulate miRNA via triple-interaction (electrostatic, hydrogen bond and hydrophobic bonding) to protect miRNA against enzyme degradation in the blood, but also is capable of crossing blood brain barrier (BBB) and allowing targeted delivery of miRNAs to GBM tissue due to the dual-targeting function of Angiopep-2. Moreover, the co-delivered anti-miR-21 and miR-124 simultaneously regulated the mutant RAS/PI3K/PTEN/AKT signaling pathway in tumor cells, consequently achieving combinatorial GBM therapy. This combinatorial effect was confirmed by our results showing that these miRNA nanomedicines can effectively reduce tumor cell proliferation, migration and invasion as well as reducing tumor angiogenesis. Consequently, effective suppression of tumor growth and significantly improved medium survival time are observed when these miRNA nanomedicines were assessed in an orthotopic GBM xenograft model. This work indicated that our new polymeric nanoparticles successfully mediate inhibition of miR-21 and miR-124 supplementation to significantly reduce tumorigenesis, and may have strong potential in GBM therapy.
    Keywords:  Combinatorial therapy; Glioblastoma; Polymeric nanoparticle; ROS response; miRNA
    DOI:  https://doi.org/10.1016/j.biomaterials.2021.121036
  13. ACS Appl Bio Mater. 2020 May 18. 3(5): 3078-3086
    Stable Retinoid Analogue Targeted Dual pH-Sensitive Smart Lipid ECO/pDNA Nanoparticles for Specific Gene Delivery in the Retinal Pigment Epithelium.
    Da Sun, Rebecca M Schur, Avery E Sears, Song-Qi Gao, Wenyu Sun, Amirreza Naderi, Timothy Kern, Krzysztof Palczewski, Zheng-Rong Lu.
      
    DOI:  https://doi.org/10.1021/acsabm.0c00130
This page is being maintained by Thomas Krichel. It was last updated on 2021‒08‒02 at 07:35:03.