30 results about "Chloroquine" patented technology

AAV vectors are ideally suited for long-term delivery of a combination of broadly neutralizing antibodies to achieve sterilizing immunity to HIV. Unfortunately, host immune responses to the delivered antibody have severely limited the efficacy. The TLR9 pathway has been identified in initiating adaptive immune responses against AAV and delivered bNAbs. To enhance this strategy, we validated Hydroxychloroquine, a known drug inhibitor of the TLR9 pathway, as a pretreatment to AAV delivery to avoid anti-drug antibody responses. TLR9 signaling inhibition was validated using a HEK-Blue hTLR9 reporter cell line and CpG stimulation. Hydroxychloroquine was also validated in a 3-macaque trial where AAV9-3BNC117 and AAV9-10-1074 were administered along with 3 doses of hydroxychloroquine once a week starting 1 week before AAV inoculation. Unlike historical controls, where 3BNC117 and 10-1074 expression is lost within the first 4-5 weeks, 2 macaques maintained 10-1074 expression and 1 macaque maintained 3BNC117 for the duration of the trial. Anti-3BNC117 antibodies were only observed in 2 of the 3 macaques and were significantly delayed. Anti-10-1074 antibody responses were a log lower than typically observed in historic controls. The use of hydroxychloroquine as a pretreatment for AAV inoculation is a promising strategy. The significant decrease in anti-10-1074 antibody levels and the successful delivery of 10-1074 in 2 macaques and 3BNC117 in 1 macaque was very encouraging. Extending the dosage of hydroxychloroquine beyond 3 doses may be sufficient to observe long-term bNAb expression in all animals and further decrease ADA responses. Together, these data suggest that the short-term treatment of hydroxychloroquine at the time of AAV inoculation has a meaningful impact on tolerance induction to our AAV-delivered bNAbs.

The invention discloses a medicine for preventing or treating liver toxic and side effects of osimertinib, and belongs to the technical field of medicines. Aiming at liver toxic and side effects caused by osimertinib, the invention provides an effective therapeutic drug, and the autophagy inhibitor relieves death caused by excessive activation of an autophagy pathway in hepatocytes by inhibiting autophagy activated by osimertinib, so that hepatotoxicity caused by osimertinib is relieved. The autophagy inhibitor and osimertinib are combined, so that the survival rate of hepatocytes can be remarkably improved, and liver injury caused in the osimertinib treatment process is reduced. The invention further provides novel application of the hydroxychloroquine or the S-adenosylmethionine in preparation of the medicine for preventing or treating the liver toxic and side effects of the osimertinib, the hydroxychloroquine or the S-adenosylmethionine has a remarkable treatment effect on liver injuries caused by the osimertinib, the medication safety of the hydroxychloroquine or the S-adenosylmethionine is high, and the hydroxychloroquine or the S-adenosylmethionine can be used for preparing the medicine for preventing or treating the liver toxic and side effects of the osimertinib. Good development prospects are realized.

The present invention aims to provide a chemical mechanical polishing (CMP) slurry for tungsten polishing, comprising: a chloroquine corrosion inhibitor, water, abrasive particles, a catalyst, a stabilizer, an oxidant, and a pH adjuster. The CMP slurry provided by the present invention can provide high tungsten polishing speeds and moderate silica polishing speeds. Most importantly, the composition exhibits low tungsten static corrosion, thereby improving the surface condition of the polished metal.

The application discloses a method for recycling 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane, which comprises the following steps: 1) adjusting the pH value of wastewater to 12-14 to obtain a first mixed solution; 2) adding an organic solvent to the first mixed solution for extraction to obtain an organic phase containing 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane; 3) performing vacuum concentration on the organic phase to obtain a concentrated solution; and 4) performing vacuum distillation on the concentrated solution, heating to 195-210 DEG C, and collecting a fraction at 190-200 DEG C to obtain 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane, wherein the wastewater is generated in the post-treatment stage of an amination reaction of hydroxychloroquine synthesis, and the organic solvent is at least one selected from dichloromethane, toluene and ethyl acetate. Thus, 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane in the wastewater can be recycled, the purity of the recycled substance reaches 98% or above, the recycled 5-(N-ethyl-N-hydroxyethyl)-2-aminopentane can be reused, and a large amount of production cost can be saved.

The present invention discloses the use of hydroxychloroquine sulfate in the preparation of a medicament for preventing and treating porcine reproductive and respiratory syndrome. The present invention discloses that hydroxychloroquine sulfate has a significant effect against porcine reproductive and respiratory syndrome virus. Its maximum non-toxic dose is 100 μM, which can effectively inhibit the infection and proliferation of porcine reproductive and respiratory syndrome virus and has a good therapeutic effect on PRRSV infection in piglets. It can be used as a medicament for preventing and treating porcine reproductive and respiratory syndrome and has good application prospects in the prevention and treatment of porcine reproductive and respiratory syndrome.

The invention discloses a composition with a tumor mitochondrial dual regulation effect, temperature-sensitive hydrogel and application, and belongs to the technical field of biological medicine, the composition is composed of a peroxide initiator and a mitochondrial autophagy inhibitor, the peroxide initiator is used for causing mitochondrial damage, and the mitochondrial autophagy inhibitor is used for causing mitochondrial autophagy. The mitochondrial autophagy inhibitor is used for inhibiting mitochondrial The peroxide initiator is indocyanine green, chlorin, iron oxide nanoparticles or Fe-MOFs (Metal-Organic Frameworks); the mitochondrial autophagy inhibitor is chloroquine, 3-methyladenosine or bajulomycin A1; the tumor is specifically melanoma; the combination of the peroxide initiator and the mitochondrial autophagy inhibitor can better inhibit the energy metabolism of tumor cells and inhibit the occurrence and development of tumors, and after the composition is delivered through the temperature-sensitive hydrogel carrier, the treatment effect of the composition on tumors is further improved.

The invention discloses application of hydroxychloroquine to improvement of gene editing efficiency. The invention provides novel application of hydroxychloroquine, namely application of hydroxychloroquine in improving gene editing efficiency of a gene editing reagent on a receptor biological material. In the prior art, a research of combining hydroxychloroquine and gene editing efficiency is not seen. The inventor of the invention finds that the gene editing efficiency can be remarkably improved by treating a receptor biological material with hydroxychloroquine and then transfecting a gene editing reagent. The method is easy and convenient to operate and wide in applicability, and a new way for improving the editing efficiency is developed by introducing exogenous small molecules instead of directly modifying a gene editing tool. The invention provides a basis for exploring an editing efficiency improvement strategy by adding exogenous molecules instead of modifying an editor mutant.

The application provides a preparation method and application of a double-membrane fusion targeted nano drug delivery system, a targeted material Cholesterol-PEG2000-RT modified liposome loaded with hydroxychloroquine is prepared, then the similarity of the liposome and the membrane component of the exosome is utilized, and the fusion of the two is realized through an extrusion method, so that the double-membrane fusion targeted drug delivery system for activating hepatic stellate cells is prepared. The double-membrane fusion targeted nano drug delivery system can not only exert the synergistic anti-hepatic fibrosis treatment effect of hydroxychloroquine and the exosome, but also can realize the specific targeted autophagy inhibition of hydroxychloroquine on activated hepatic stellate cells, so that the further proliferation and differentiation of the activated hepatic stellate cells are prevented, the generation of fibrosis-related proteins is reduced, the anti-hepatic fibrosis effect is exerted, and in addition, the genes and active factors carried by the exosome derived from bone marrow mesenchymal stem cells can exert the liver protection and synergistic anti-hepatic fibrosis effect, so that a new thought and method are provided for the clinical treatment of hepatic fibrosis.

The invention discloses an osthole compound pesticide composition for preventing and treating plant pathogenic fungi and application of the osthole compound pesticide composition. The composition comprises an effective component A and an effective component B, the effective component A is cnidium lactone, and the effective component B is eugenol, azoxystrobin or hydroxychloroquine. The composition is compounded by using the cnidium lactone and eugenol, the cnidium lactone and azoxystrobin as well as the cnidium lactone and hydroxychloroquine as effective components, so that the composition has an obvious synergistic effect on preventing and treating tea leaf spot and tomato gray mold, and the generation of drug resistance and drug resistance of plants can be delayed by compounding the effective components; more choices are provided for prevention and treatment of pathogenic fungi, and the bacillus subtilis has a wide application prospect in prevention and treatment of plant pathogenic fungi diseases.

The invention belongs to the technical field of biological medicines, and particularly relates to a marker for evaluating the curative effect of hydroxychloroquine on treating IgA nephropathy and application of the marker. The marker for evaluating the curative effect of the hydroxychloroquine on the IgA nephropathy is a combination of any one or any two or any three or any four or five of D-ornithine, L-arginine, L-cysteine, L-cystine and D-cysteine. Based on the five markers, a combined prediction model is constructed, the model shows relatively high prediction performance, and an early-stage non-invasive screening method can be provided for clinic and is used for identifying IgAN patients with potential HCQ treatment ineffectiveness.

The present invention relates to a pharmaceutical composition for preventing or treating flavivirus infections. The invention provides a pharmaceutical composition. The pharmaceutical composition comprises at least one of gentamicin sulfate, netilmicin, tobramycin, paromomycin, amikacin, capreomycin, triflurazine, dihydrostreptomycin, hydroxychloroquine, thiolidazine hydrochloride, efavirenz, mitefonew, nystatin, micafungin, bleomycin, remistat, montelukast, norfloxacin, nedaplatin and cephalosporin, and the pharmaceutical composition is prepared from the following raw materials in parts by weight. It is possible to exhibit an excellent growth inhibition or inactivation effect on different species of flavivirus.

The invention discloses a bridged biquinoline compound and a preparation method and application thereof.The compound has a certain killing effect on colon cancer cells, lung cancer cells, liver cancer cells, gastric cancer cells, cervical cancer cells and breast cancer cells, the killing effect on the colon cancer cells is especially obvious, and the killing effect on the colon cancer cells is remarkably superior to that of positive control drugs chloroquine and cis-platinum; in addition, the bridged biquinoline compound has small toxic and side effects, solves the problem of large toxic and side effects of traditional platinum antitumor drugs such as cis-platinum and the like, and can be prepared into antitumor drugs for application. The preparation method of the bridged biquinoline compound is simple and efficient, industrial production can be realized, and the bridged biquinoline compound has great application value in tumor resistance.

A composition for preventing or treating a TNF-α-related disease is disclosed. The composition includes hydroflumethiazide or a pharmaceutically acceptable salt thereof as an active ingredient. The composition can effectively inhibit the expression or activity of TNF-α and exhibits an excellent treatment effect compared to methotrexate (MTX) or hydroxychloroquine (HCQ), which are rheumatoid arthritis treatment agents currently on the market, and, thus, can be effectively used for prevention or treatment of a TNF-α-related disease.

The invention relates to the technical field of biological medicines, in particular to application of veratramine in preparation of lysosome capture inhibition preparations and antiviral preparations. It is found that veratramine can be captured by lysosome and accumulated in the lysosome, and veratramine can be used for preparing lysosome capture inhibition preparations. Veratrolamine has the characteristics of small toxic and side effects and high safety, and is obviously superior to the existing lysosome capture inhibitors such as chloroquine and the like.

The invention discloses a double-membrane independently wrapped nano drug delivery system for regulating macrophages and platelets. The nano drug delivery system comprises macrophage membrane coated nanoparticles and platelet membrane coated nanoparticles, the macrophage membrane coated nanoparticles are used for adjusting macrophage immune response and loaded with a Toll-like receptor 7 (TLR7) inhibitor, the platelet membrane coated nanoparticles are used for inhibiting abnormal activation of platelets and loaded with a G protein coupled receptor P2Y12 inhibitor, the TLR7 inhibitor comprises at least one of TJ-M2010-5, hydroxychloroquine, Enpatron and IMO-8400, and the TLR7 inhibitor comprises at least one of TJ-M2010-5, hydroxychloroquine, Enpatron and IMO-8400. The P2Y12 inhibitor is prepared from at least one of ticagrelor, clopidogrel, prasugrel and cangrelor. According to the double-membrane independently-wrapped nano drug delivery system, drugs are efficiently delivered to related damaged cells of an inflammation part by utilizing related cell tropism of two cell membranes, immune disorder caused by macrophage and platelet abnormality is inhibited, diseases induced by immune imbalance are treated, an immune microenvironment is regulated and controlled, and the drug delivery effect is improved. And a new direction is provided for treatment of immune diseases.

The invention provides a method for treating systemic lupus erythematosus through a hydroxychloroquine soluble microneedle, and relates to the field of lupus erythematosus treatment.The method comprises the steps that S100, a hydroxychloroquine (HCQ) soluble microneedle patch is prepared, a mixture of hyaluronic acid and polyvinyl alcohol (PVA) serves as a soluble matrix of the microneedle patch, hydroxychloroquine is evenly loaded in the matrix, and the height of the microneedle is 300-1000 micrometers; according to the application, the microneedle penetrates through the cuticle to directly deliver the hydroxychloroquine to the subcutaneous target region, the first-pass effect and whole body exposure of oral administration are avoided, the retina toxicity and gastrointestinal tract side effects of the hydroxychloroquine are reduced, the height of the microneedle is controlled to be 500-800 microns, the microneedle only penetrates through the epidermal layer and does not touch nerve endings, and painless administration is realized; a patient can operate by himself / herself without assistance of professional medical personnel, a cross-linked structure of hyaluronic acid and a PVA matrix can realize slow release of hydroxychloroquine, and a highly expressed hyaluronic acid receptor at a lupus erythematosus lesion site is targeted through anti-CD44 antibody modification.

The invention discloses a tumor targeted quantum dot as well as a preparation method and application thereof. The method comprises the following steps: S1, preparing a CuInSe2 quantum dot; s2, Ag-CISe / ZnS QDs (Quantum Dots) are prepared; s3, the Ag-CISe / ZnS QDs are modified with folic acid, and Ag-CISe / ZnS / FA QDs are obtained; and S4, modifying hydroxychloroquine on the Ag-CISe / ZnS / FA QDs, so as to obtain Ag-CISe / ZnS / FA / CQ QDs, namely the tumor targeting type quantum dot. The tumor targeting type quantum dot prepared by the invention has the characteristic of targeting tumor cells, has excellent photo-thermal performance, and has huge potential of being combined with a photo-thermal treatment method to be applied to anti-tumor treatment; and a low-cost water-phase synthesis method enhances the clinical application value, and an effective treatment preparation can be provided for mild photo-thermal cancer treatment.

The invention discloses application of CREG1 in preparation of a medicine for treating spontaneous abortion caused by hyperhomocysteinemia (HHcy), and belongs to the technical field of biological medicine. Experiments show that the CREG1 is highly expressed in villus tissue trophoblastic cells of HHcy combined with spontaneous abortion, cell viability decline caused by DL-hcy can be effectively improved by inhibiting expression of the CREG1, embryo absorption and placenta dysfunction caused by HHcy can be improved by targeted intervention of the CREG1, and the CREG1 can be used as a key target of drugs for high-throughput screening of HHcy-induced spontaneous abortion and can be used for preparing drugs for treating HHcy-induced spontaneous abortion. Wide application prospects are realized; the sh-CREG1 lentivirus, chloroquine and the derivative of chloroquine are used for treating the spontaneous abortion caused by HHcy, and a brand new solution is provided for clinic.

Despite recent efforts to eradicate malaria worldwide, this parasitic disease is still considered a major public health problem, with a total of 219 million malaria cases and 435,000 deaths in 2017 After a decade of use, however, resistance to CQ has emerged in some locations, including Southeast Asia, South America, and the Western Pacific region, spreading progressively into malaria-endemic areas, including Africa, where increases in malaria mortality have been observed. This has led, in recent years, to the adoption of artemisinin-based combination therapies. Artemisinin-based combination therapies remain effective in most parts of the world, but recent cases of resistance in Southeast Asia call for new approaches and especially new drugs to treat malaria. Thus, the present invention features CQ analogues of Formula (I) that exhibited high activity against CQ-sensitive and CQ-resistant blood parasites and were also active in mice. The present invention also provides pharmaceutical compositions comprising the compounds of Formula (I), use of said compounds, and methods for treating conditions caused by blood parasites.

The invention discloses a method for preparing exosomes by simulating a low-density lipoprotein cholesterol standard-exceeding environment, and relates to the technical field of exosomes, and the method comprises the following steps: inoculating umbilical cord mesenchymal stem cells into a culture plate, after the cell fusion degree reaches 85%, adding chloroquine-liposome, and culturing for 24-48 hours; collecting cell supernate, and extracting exosomes by adopting an ultracentrifugation method; the chloroquine lipidosome is obtained by fusing lipidosome and chloroquine and then performing freeze thawing treatment, the lipidosome is prepared from phospholipid, low-density lipoprotein, low-density protein cholesterol and mesoporous silica nanoparticles through a film dispersion method, and vitamin E is further loaded in the mesoporous silica nanoparticles; the problem of liposome burst release caused by ph change can be solved, a more stable chloroquine release process is realized, and the problem that the exosome yield and the treatment effect cannot be considered at the same time is solved.

The invention discloses an application of combination of tripterine and chloroquine in preparation of an antitumor drug. The antitumor drug comprises tripterine and chloroquine. The combined application of the tripterine and the chloroquine has stronger anti-tumor activity than a single component, and the combined pharmaceutical composition can significantly enhance the ICD effect, prolong the lifetime of tumor-bearing mice, and provide a new method and thought for cancer treatment.

The application provides an activated endothelial cell membrane-coated nanoparticle, a preparation method, application and a pharmaceutical composition, and belongs to the technical field of biomedical materials. The nanoparticle is composed of a rutin / hydroxychloroquine self-assembled nanoparticle core coated by brain microvascular endothelial cell membranes pretreated by TNF-alpha. The application screens a specific molar ratio of rutin and hydroxychloroquine. The preparation can be combined with the specific binding of ICAM-1 and integrin alpha M beta2 on the surface of neutrophils, and can be carried by neutrophils to cross the blood-brain barrier, realize parenchymal brain targeting enrichment, and synergistically exert anti-inflammatory, antioxidant, NETs formation inhibition and neuroprotective effects, thereby significantly improving ischemic stroke reperfusion injury.

The invention relates to the field of biomedicine, and discloses application of an HLA-B * 27: 04 allele in preparation of a product for evaluating the risk of drug rash caused by hydroxychloroquine. The application comprises the step of predicting the medication risk of a subject by detecting whether the subject carries the HLA-B * 27: 04 allele or not. The HLA-B * 27: 04 allele is found to be strongly related to the drug rash caused by the hydroxychloroquine for the first time and can be used as a risk genetic marker of the drug rash caused by the hydroxychloroquine. In practical application, the risk of drug eruption of a subject needing to be treated by using hydroxychloroquine can be predicted by detecting whether the HLA-B * 27: 04 allele is carried by the subject, and the risk of drug eruption caused by hydroxychloroquine of the subject carrying the HLA-B * 27: 04 allele after the subject uses hydroxychloroquine is obviously higher than that of a non-carrier. The detection product provided by the invention is high in specificity, high in positive predictive value and good in clinical application prospect.

The invention discloses a preparation method and application of a dual-targeting hepatocellular carcinoma nano-drug, and belongs to the field of biological medicines. According to the invention, a double-targeting target molecule with myeloperoxidase-asialoglycoprotein receptor double-targeting property is synthesized, and the double-targeting target molecule is modified on a covalent organic nano molecule COF-366 through pi-pi stacking, wherein the covalent organic nano molecule COF-366 is coated with chemotherapeutic drugs sorafenib and chloroquine and has photodynamic characteristics. The obtained nano-drug can be gradually delivered to hepatocytes under the guidance of double-targeting molecules, drug release is started in acidity of a tumor acidic microenvironment, the synergistic treatment effect of photodynamic therapy and chemotherapy can be played, and the synergistic effect causes tumor injury, so that the inflammation targeting of the nano-drug is further enhanced. The nano-drug has good stability and biological safety, in-vivo behavior tracing and treatment efficacy evaluation are carried out in subcutaneous solid tumor and in-situ tumor mouse models, and the nano-drug is expected to play a huge role in clinical application.

The present invention discloses a compound having a hydroxychloroquine tetravalent platinum structure, a preparation method thereof, and an application thereof. The compound having a hydroxychloroquine tetravalent platinum structure provided by the present invention has a structure as shown in formula (1). The present invention introduces hydroxychloroquine, which has the ability to inhibit autophagy, into a tetravalent platinum structure, and designs and prepares a hydroxychloroquine tetravalent platinum complex. This type of compound exerts an anti-tumor effect through a synergistic anti-cancer mechanism of DNA damage, autophagy inhibition, tumor microenvironment regulation, and immune activation, overcoming the problem of drug resistance of current divalent platinum (II) drugs, significantly improving anti-tumor activity, and reducing toxicity. It is a new type of platinum (IV) drug with the potential to inhibit tumor proliferation and tumor metastasis.

The application discloses a kind of double sulfur vacancy SV-Bi2S3 / SV-ZnIn2S4 heterojunction photocatalyst and preparation method and application.The double sulfur vacancy SV-Bi2S3 / SV-ZnIn2S4 composite photocatalyst, the existence of sulfur vacancy in composite material is confirmed by electron paramagnetic resonance.In addition, scanning electron microscopy, X-ray diffraction and fourier infrared analysis show that these results show that there is interaction between composite material and has close interface contact.In addition, the double sulfur vacancy SV-Bi2S3 / SV-ZnIn2S4 composite photocatalyst prepared by the application has good structural stability, and the characteristics of repeated use greatly reduce the processing cost.Further, the catalyst is low in cost, can quickly decompose and convert chloroquine phosphate in wastewater, greatly improves the efficiency of wastewater treatment, and meets the needs of large-scale industrial application.

The invention discloses application of attapulgite in recovery of lysosome acidity and autophagy flux, and belongs to the field of nano biotechnology medicine. The invention finds that attapulgite can recover lysosome acidity decrease caused by lipotoxicity, chloroquine, lysosome inhibitors and the like and recover blocked autophagy flux. The invention finds that ATT can effectively regulate cytotoxicity of chloroquine and recover lysosome acidity decrease and blocked autophagy flow caused by chloroquine or lipotoxicity. Besides, ATT shows a remarkable treatment effect on lysosomal dysfunction related diseases such as NAFLD, lysosomal acidity and autophagy flow in a high-fat feeding induced NAFLD model can be recovered, lipid accumulation and liver biochemical indexes can be effectively reduced, and the tolerance of glucose can be improved. In addition, the activity of lysosome hydrolase can be increased, and degradation of mutant huntingtin is accelerated.

The present application relates to the technical field of medicine, and particularly discloses application of chiral hydroxychloroquine or a pharmaceutically acceptable salt thereof in preparation of a drug for preventing and treating immune diseases. The chiral hydroxychloroquine or the pharmaceutically acceptable salt thereof has a better inhibition rate and a lower cell survival rate on pathological cell proliferation caused by immune diseases, including but not limited to fibroblast-like synoviocytes; the chiral hydroxychloroquine or the salt thereof combined with methotrexate / ilaris (including but not limited to) can reduce the toxic side effects on normal cells and the cell survival rate, and has a better treatment effect on immune diseases.

This invention provides methods for treating acute respiratory distress syndrome (ARDS), including ARDS associated with respiratory viral infections. [Solution] Administer plasma kallikrein (pKal) inhibitors such as anti-pKal antibodies as inhibitors of the contact activation pathway. Immunomodulators such as IL-6R inhibitors, antiviral agents such as lopinavir, ritonavir, interferon beta, umfenovir, and remdesivir, antimalarial agents such as chloroquine, and / or inhibitors of the contact activation pathway such as C1 inhibitors, pKal inhibitors, and bradykinin receptor antagonists may be administered to the patient as additional therapeutic agents.

AAV vectors are ideally suited for long-term delivery of a combination of broadly neutralizing antibodies to achieve sterilizing immunity to HIV. Unfortunately, host immune responses to the delivered antibody have severely limited the efficacy. The TLR9 pathway has been identified in initiating adaptive immune responses against AAV and delivered bNAbs. To enhance this strategy, we validated Hydroxychloroquine, a known drug inhibitor of the TLR9 pathway, as a pretreatment to AAV delivery to avoid anti-drug antibody responses. TLR9 signaling inhibition was validated using a HEK-Blue hTLR9 reporter cell line and CpG stimulation. Hydroxychloroquine was also validated in a 3-macaque trial where AAV9-3BNC117 and AAV9-10-1074 were administered along with 3 doses of hydroxychloroquine once a week starting 1 week before AAV inoculation. Together, these data suggest that the short-term treatment of hydroxychloroquine at the time of AAV inoculation has a meaningful impact on tolerance induction to our AAV-delivered bNAbs.