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Human papillomavirus (HPV) vaccination represents a milestone in primary prevention of sexually transmitted infections. However, little is known about its possible effects on already established HPV infections. We report the case of a 9-year-old immunosuppressed girl with refractory warts, successfully treated with the nonavalent-HPV vaccine and review the literature about the therapeutic effects of HPV vaccination on benign HPV-induced epithelial proliferations in immunocompetent and immunosuppressed patients. In the literature, promising results were shown on cutaneous warts after HPV vaccination, especially in children and young adults, also in immunosuppressed patients, whereas controverse results were found on anogenital warts. These findings suggest a critical need for randomized clinical trials to assess the efficacy of HPV vaccination in the treatment of benign HPV-induced epithelial proliferations.
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DNASE1L3 is an extracellular nuclease that digests chromatin released from apoptotic cells. DNASE1L3 mutations impair the enzyme function, enhance autoantibody production and type I interferon (IFN-I) responses, and cause different autosomal recessive phenotypes ranging from hypocomplementemic urticarial vasculitis syndrome to full-blown systemic lupus erythematosus (SLE). Kidney involvement in patients with DNASE1L3 mutations is poorly characterised. Herein, we describe the clinical course of three children with monogenic SLE due to DNASE1L3 mutations who developed refractory glomerulonephritis leading to kidney failure. They had different renal histopathological patterns (i.e., membranous, endo- and extra-capillary glomerulonephritis and thrombotic microangiopathy), all belonging to the lupus nephritis (LN) spectrum. One patient had a mixed phenotype, showing an overlap between SLE and ANCA-associated vasculitis. Using immunofluorescence, we detected glomerular expression of the IFN I-induced human myxovirus resistance protein 1 (MXA), which was particularly evident in glomerular endothelial cells. 2/3 patients had increased expression of interferon-stimulated genes in the peripheral blood and all three patients had reduced serum DNAse activity. Our findings suggest that DNASE1L3-related glomerulonephritis can be included in the spectrum of IFN I-mediated kidney disorders, and provide the rationale for IFN I-directed therapies in order to improve the poor outcome of this rare condition.
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Up to 70% of patients with Wiskott-Aldrich Syndrome (WAS) develop autoimmune and inflammatory manifestations. Dysregulation of interleukin (IL)-1 may be involved in their pathogenesis, yet there is little evidence on treatment with anti-IL-1 agents in these patients. We conducted a multicenter retrospective analysis of nine patients with WAS treated with anti-IL-1 agents (anakinra or canakinumab). All patients had prominent inflammatory manifestations, including systemic, cutaneous, articular, and intestinal symptoms; three patients presented with a severe systemic inflammatory syndrome since the first months of life. Corticosteroid therapy was associated with partial or no response, while treatment with anakinra or canakinumab resulted in prompt, often dramatic, responses in all patients, allowing bridging to gene therapy (four patients) or hematopoietic stem cell transplantation (HSCT, five patients). Treatment was overall well tolerated. Low donor myeloid chimerism developed in four patients after HSCT and was associated with the appearance or the recurrence of inflammatory manifestations. A second HSCT was performed in two patients, achieving full-donor chimerism and resolution of inflammatory manifestation, while the other two patients were treated with prolonged therapy with anti-IL-1 agents. Our experience demonstrates that some inflammatory manifestations of WAS are dependent on IL-1 and respond very well to its pharmacologic blockade.
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Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2.
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Tronco Encefálico , COVID-19 , Neuronas , SARS-CoV-2 , Humanos , Masculino , SARS-CoV-2/genética , COVID-19/genética , COVID-19/virología , Tronco Encefálico/patología , Tronco Encefálico/virología , Tronco Encefálico/metabolismo , Adolescente , Neuronas/metabolismo , Neuronas/patología , Encefalitis Viral/genética , Encefalitis Viral/patología , Encefalitis Viral/virología , Fibroblastos/metabolismo , Rombencéfalo/metabolismoAsunto(s)
Azetidinas , Purinas , Pirazoles , Sulfonamidas , Humanos , Pirazoles/uso terapéutico , Azetidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Purinas/uso terapéutico , Masculino , Femenino , Niño , Preescolar , MutaciónRESUMEN
[This corrects the article DOI: 10.3389/fneph.2023.1194989.].
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Deposition of autoantibodies in glomeruli is a key factor in the development of lupus nephritis (LN). For a long time, anti-dsDNA and anti-C1q antibodies were thought to be the main cause of the kidney damage. However, recent studies have shown that the list of autoantibidies that have renal tropism and deposit in the kidney in LN is increasing and the link between anti-dsDNA and renal pathology is weak due to potential confounders. Aspecific bindings of dsDNA with cationic antibodies and of anti-dsDNA with several renal antigens such as actinin, laminin, entactin, and annexinA2 raised doubts about the specific target of these antibodies in the kidney. Moreover, the isotype of anti-dsDNA in SLE and LN has never received adequate interest until the recent observation that IgG2 are preponderant over IgG1, IgG3 and IgG4. Based on the above background, recent studies investigated the involvement of anti-dsDNA IgG2 and of other antibodies in LN. It was concluded that circulating anti-dsDNA IgG2 levels do not distinguish between LN versus non-renal SLE, and, in patients with LN, their levels do not change over time. Circulating levels of other antibodies such as anti-ENO1 and anti-H2 IgG2 were, instead, higher in LN vs non-renal SLE at the time of diagnosis and decreased following therapies. Finally, new classes of renal antibodies that potentially modify the anti-inflammatory response in the kidney are emerging as new co-actors in the pathogenetic scenario. They have been defined as 'second wave antibodies' for the link with detoxifying mechanisms limiting the oxidative stress in glomeruli that are classically stimulated in a second phase of inflammation. These findings have important clinical implications that may modify the laboratory approach to LN. Serum levels of anti-ENO1 and anti-H2 IgG2 should be measured in the follow up of patients for designing the length of therapies and identify those patients who respond to treatments. Anti-SOD2 could help to monitor and potentiate the anti-inflammatory response in the kidney.
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Autoanticuerpos , Nefritis Lúpica , Nefritis Lúpica/inmunología , Nefritis Lúpica/diagnóstico , Humanos , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Animales , Anticuerpos Antinucleares/inmunología , Anticuerpos Antinucleares/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina G/sangre , Autoantígenos/inmunologíaRESUMEN
TLR7 recognizes pathogen-derived single-stranded RNA (ssRNA), a function integral to the innate immune response to viral infection. Notably, TLR7 can also recognize self-derived ssRNA, with gain-of-function mutations in human TLR7 recently identified to cause both early-onset systemic lupus erythematosus (SLE) and neuromyelitis optica. Here, we describe two novel mutations in TLR7, F507S and L528I. While the L528I substitution arose de novo, the F507S mutation was present in three individuals from the same family, including a severely affected male, notably given that the TLR7 gene is situated on the X chromosome and that all other cases so far described have been female. The observation of mutations at residues 507 and 528 of TLR7 indicates the importance of the TLR7 dimerization interface in maintaining immune homeostasis, where we predict that altered homo-dimerization enhances TLR7 signaling. Finally, while mutations in TLR7 can result in SLE-like disease, our data suggest a broader phenotypic spectrum associated with TLR7 gain-of-function, including significant neurological involvement.
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Mutación con Ganancia de Función , Lupus Eritematoso Sistémico , Femenino , Masculino , Humanos , Receptor Toll-Like 7 , Mutación , Dimerización , ARNRESUMEN
Gain-of-function mutations in NLRP3 are linked to cryopyrin-associated periodic syndromes (CAPS). Although NLRP3 autoinflammasome assembly triggers inflammatory cytokine release, its activation mechanisms are not fully understood. Our study used a functional genetic approach to identify regulators of NLRP3 inflammasome formation. We identified the HSP90ß-SGT1 chaperone complex as crucial for autoinflammasome activation in CAPS. A deficiency in HSP90ß, but not in HSP90α, impaired the formation of ASC specks without affecting the priming and expression of inflammasome components. Conversely, activating NLRP3 with stimuli such as nigericin or alum bypassed the need for SGT1 and HSP90ß, suggesting the existence of alternative inflammasome assembly pathways. The role of HSP90ß was further demonstrated in PBMCs derived from CAPS patients. In these samples, the pathological constitutive secretion of IL-1ß could be suppressed using a pharmacological inhibitor of HSP90ß. This finding underscores the potential of SGT1-HSP90ß modulation as a therapeutic strategy in CAPS while preserving NLRP3's physiological functions.
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Síndromes Periódicos Asociados a Criopirina , Proteína con Dominio Pirina 3 de la Familia NLR , Humanos , Síndromes Periódicos Asociados a Criopirina/genética , Síndromes Periódicos Asociados a Criopirina/tratamiento farmacológico , Síndromes Periódicos Asociados a Criopirina/patología , Citocinas , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genéticaRESUMEN
Syndrome of undifferentiated recurrent fever (SURF) is characterized by recurrent fevers, a lack of confirmed molecular diagnosis, and a complete or partial response to colchicine. Despite the clinical similarities to familial Mediterranean fever (FMF), the underlying inflammatory mechanisms of SURF are not yet understood. We here analyzed the in vitro activation of the pyrin inflammasome in a cohort of SURF patients compared to FMF and PFAPA patients. Peripheral blood mononuclear cells (PBMC) were collected from SURF (both colchicine-treated and untreated), FMF, PFAPA patients, and healthy donors. PBMC were stimulated ex vivo with Clostridium difficile toxin A (TcdA) and a PKC inhibitor (UCN-01), in the presence or absence of colchicine. The assembly of the pyrin inflammasome was evaluated by measuring the presence of apoptosis-associated Speck-like protein containing caspase recruitment domain (ASC) specks in monocytes using flow cytometry. IL-1ß secretion was quantified using an ELISA assay. No differences in TcdA-induced activation of pyrin inflammasome were observed among FMF, PFAPA, and healthy donors. Untreated SURF patients showed a reduced response to TcdA, which was normalized after colchicine treatment. In contrast to FMF, SURF patients, similar to PFAPA patients and healthy donors, did not exhibit pyrin inflammasome activation in response to UCN-01-mediated pyrin dephosphorylation. These data demonstrate that in vitro functional analysis of pyrin inflammasome activation can differentiate SURF from FMF and PFAPA patients, suggesting the involvement of the pyrin inflammasome in the pathophysiology of SURF.
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Colchicina , Fiebre Mediterránea Familiar , Humanos , Colchicina/farmacología , Colchicina/uso terapéutico , Fiebre Mediterránea Familiar/diagnóstico , Fiebre Mediterránea Familiar/tratamiento farmacológico , Inflamasomas , Leucocitos Mononucleares , Pirina/genéticaRESUMEN
BACKGROUND: Janus kinase inhibitors are antirheumatic immunosuppressive drugs that target intracellular Janus kinases (JAKs). Baricitinib is a selective and reversible orally administered JAK1/JAK2 inhibitor approved for treating rheumatoid arthritis, atopic dermatitis, and alopecia areata in adult patients. Expanded access to baricitinib has been approved for treating pediatric patients affected by rare Mendelian autoinflammatory diseases with type I interferon-mediated damage. Knowledge of the pharmacokinetic properties and target plasma levels of baricitinib in pediatric patients is limited. In this study, a novel LC-MS/MS method for measuring baricitinib in plasma, validated according to the ICH M10 guidelines, is presented. METHODS: Sample preparation was performed by adding 10 µL of IS working solution (150 ng/mL) and 200 µL of MeOH to each plasma sample. Chromatographic separation was conducted using a Thermo Scientific Accucore Polar Premium column (50 mm × 2.1 mm, i.d. 2.6 m). This method was applied to 7 real anonymous plasma samples obtained from pediatric patients treated with baricitinib at IRCCS Istituto Giannina Gaslini (Genoa, Italy). Patients of both sexes had a median age of 14 years (range, 10-17 years). RESULTS: The LC-MS/MS method resulted linear over wide concentration ranges (1.024-100 ng/mL) and was accurate and reproducible in the absence of matrix effects, allowing for robust, specific, and rapid quantification of baricitinib from a low amount of plasma (50 µL). The plasma concentration of baricitinib in the samples of the patients, expressed as mean ± SD, was 11.25 ± 10.86 ng/mL. CONCLUSIONS: This novel LC-MS/MS method is suitable for the therapeutic drug monitoring of baricitinib and can help guide therapy optimization in pediatric patients.
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Antirreumáticos , Inhibidores de las Cinasas Janus , Masculino , Adulto , Femenino , Humanos , Niño , Adolescente , Cromatografía Liquida , Cromatografía Líquida con Espectrometría de Masas , Monitoreo de Drogas , Espectrometría de Masas en Tándem , Inhibidores de las Cinasas Janus/farmacocinética , Inhibidores de las Cinasas Janus/uso terapéutico , Antirreumáticos/uso terapéuticoRESUMEN
BACKGROUND: To date, no publicly accessible platform has captured and synthesized all of the layered dimensions of genotypic, phenotypic, and mechanistic information published in the field of inborn errors of immunity (IEIs). Such a platform would represent the extensive and complex landscape of IEIs and could increase the rate of diagnosis in patients with a suspected IEI, which remains unacceptably low. OBJECTIVE: Our aim was to create an expertly curated, patient-centered, multidimensional IEI database that enables aggregation and sophisticated data interrogation and promotes involvement from diverse stakeholders across the community. METHODS: The database structure was designed following a subject-centered model and written in Structured Query Language (SQL). The web application is written in Hypertext Preprocessor (PHP), Hypertext Markup Language (HTML), Cascading Style Sheets (CSS), and JavaScript. All data stored in the Genetic Immunology Advisor (GenIA) are extracted by manually reviewing published research articles. RESULTS: We completed data collection and curation for 24 pilot genes. Using these data, we have exemplified how GenIA can provide quick access to structured, longitudinal, more thorough, comprehensive, and up-to-date IEI knowledge than do currently existing databases, such as ClinGen, Human Phenotype Ontology (HPO), ClinVar, or Online Mendelian Inheritance in Man (OMIM), with which GenIA intends to dovetail. CONCLUSIONS: GenIA strives to accurately capture the extensive genetic, mechanistic, and phenotypic heterogeneity found across IEIs, as well as genetic paradigms and diagnostic pitfalls associated with individual genes and conditions. The IEI community's involvement will help promote GenIA as an enduring resource that supports and improves knowledge sharing, research, diagnosis, and care for patients with genetic immune disease.
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Bases de Datos Genéticas , Programas Informáticos , HumanosRESUMEN
Juvenile systemic lupus erythematosus (jSLE) is a complex inflammatory autoimmune disorder. In the last decades, genetic factors and activation pathways have been increasingly studied to understand their potential pathogenetic role better. Genetic and transcriptional abnormalities directly involved in the type I interferon (IFN) signaling cascade have been identified through family-based and genome-wide association studies. IFNs trigger signaling pathways that initiate gene transcription of IFN-stimulated genes through the activation of JAK1, TYK2, STAT1, and STAT2. Thus, the use of therapies that target the IFN pathway would represent a formidable advance in SLE. It is well known that JAK inhibitors have real potential for the treatment of rheumatic diseases, but their efficacy in the treatment of SLE remains to be elucidated. We report the case of a 13-year-old girl affected by jSLE, carrying a novel heterozygous missense variant on Three prime Repair EXonuclease 1 (TREX1), successfully treated with baricitinib on top of mofetil mycophenolate. The TREX1 gene plays an important role in DNA damage repair, and its mutations have been associated with an overproduction of type 1 interferon. This report underlines the role of translational research in identifying potential pathogenetic pathways in rare diseases to optimize treatment.
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Interferón Tipo I , Inhibidores de las Cinasas Janus , Lupus Eritematoso Sistémico , Femenino , Humanos , Adolescente , Inhibidores de las Cinasas Janus/uso terapéutico , Estudio de Asociación del Genoma Completo , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/genética , Mutación , Interferón Tipo I/genéticaRESUMEN
Type I interferon (IFN) signalling is tightly controlled. Upon recognition of DNA by cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING) translocates along the endoplasmic reticulum (ER)-Golgi axis to induce IFN signalling. Termination is achieved through autophagic degradation or recycling of STING by retrograde Golgi-to-ER transport. Here, we identify the GTPase ADP-ribosylation factor 1 (ARF1) as a crucial negative regulator of cGAS-STING signalling. Heterozygous ARF1 missense mutations cause a previously unrecognized type I interferonopathy associated with enhanced IFN-stimulated gene expression. Disease-associated, GTPase-defective ARF1 increases cGAS-STING dependent type I IFN signalling in cell lines and primary patient cells. Mechanistically, mutated ARF1 perturbs mitochondrial morphology, causing cGAS activation by aberrant mitochondrial DNA release, and leads to accumulation of active STING at the Golgi/ERGIC due to defective retrograde transport. Our data show an unexpected dual role of ARF1 in maintaining cGAS-STING homeostasis, through promotion of mitochondrial integrity and STING recycling.
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Interferón Tipo I , Humanos , Factor 1 de Ribosilacion-ADP/genética , Factor 1 de Ribosilacion-ADP/metabolismo , Interferón Tipo I/metabolismo , Proteínas de la Membrana/metabolismo , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , Transducción de SeñalRESUMEN
OBJECTIVES: to evaluate whether the heterogeneous skin manifestations might influence the disease presentation and outcome of a cohort of SAPHO children. METHODS: the clinical, serological, imaging and therapeutic data of 14 SAPHO patients, followed between 2001 and 2022 at the Unit for Autoinflammatory diseases at the Gaslini Hospital, were reviewed. According to their cutaneous manifestations, patients were divided into 2 groups: the acne-hidradenitis suppurativa (HS) and the Palmo-Plantar Pustulosis (PPP) group. Data were retrieved from the Eurofever database. RESULTS: all patients presented bone involvement characterized by Chronic Recurrent multifocal Osteomyelitis (CRMO): 8 patients presented acne-HS while 6 patients had PPP. In the PPP group, all patients were female, characterized by a prepuberal disease onset with osteoarticular manifestations, followed by the appearance of PPP in the following 6 months. This group responded well to the treatments. In the acne-HS group, 7/8 patients were male: the disease onset was characterized by skin manifestations in pubertal age, followed by osteoarticular manifestations in the following year. This group presented a severe refractory skin disease that required in most cases the addition of biological therapies. A literature review confirmed our data highlighting the association males-acne-puberal age and female-PPP-prepuberal age. CONCLUSION: paediatric SAPHO patients should be mainly stratified according to their skin involvement. In fact, our data suggest that two different skin phenotypes may be identified in SAPHO: the first is constituted by prepuberal females with PPP and a prevalent osteoarticular involvement, while the second by puberal males with a difficult-to-treat acne-HS.
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Acné Vulgar , Síndrome de Hiperostosis Adquirido , Hidradenitis Supurativa , Osteomielitis , Humanos , Masculino , Niño , Femenino , Síndrome de Hiperostosis Adquirido/tratamiento farmacológico , PielRESUMEN
Organosilica nanoparticles that contain responsive organic building blocks as constitutive components of the silica network offer promising opportunities for the development of innovative drug formulations, biomolecule delivery, and diagnostic tools. However, the synthetic challenges required to introduce dynamic and multifunctional building blocks have hindered the realization of biomimicking nanoparticles. In this study, capitalizing on our previous research on responsive nucleic acid-based organosilica nanoparticles, we combine the supramolecular programmability of nucleic acid (NA) interactions with sol-gel chemistry. This approach allows us to create dynamic supramolecular bridging units of nucleic acids in a silica-based scaffold. Two peptide nucleic acid-based monoalkoxysilane derivatives, which self-assemble into a supramolecular bis-alkoxysilane through direct base pairing, were chosen as the noncovalent units inserted into the silica network. In addition, a bridging functional NA aptamer leads to the specific recognition of ATP molecules. In a one-step bottom-up approach, the resulting supramolecular building blocks can be used to prepare responsive organosilica nanoparticles. The supramolecular Watson-Crick-Franklin interactions of the organosilica nanoparticles result in a programmable response to external physical (i.e., temperature) and biological (i.e., DNA and ATP) inputs and thus pave the way for the rational design of multifunctional silica materials with application from drug delivery to theranostics.
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Nanopartículas , Ácidos Nucleicos , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Dióxido de Silicio/química , Adenosina TrifosfatoRESUMEN
Introduction: SARS-CoV-2 infection in the pediatric population can be associated with a multiorgan inflammatory syndrome called children's multisystem inflammatory syndrome (MIS-C). The kidneys can be affected by a broad spectrum of possible injuries, whose pathogenetic mechanisms are still unclear.Case report: We report the case of a 5-year-old boy with severe cardiac involvement in the context of MIS-C. After two weeks of hospitalization, an abdominal ultrasound showed massive bladder "debris", followed by the onset of normoglycemic glycosuria. Over time, there was a progressive increase in glycosuria, and the presence of a mat of amorphous phosphate crystals was evidenced on urinary sediment. Together with the findings of hypo-uricemia, increased urinary uric acid, and globally increased urinary amino acids, a clinical picture of kidney proximal tubular damage with secondary Fanconi-like syndrome took shape. Discussion: This case report describes the case of a patient with MIS-C with cardiac and kidney involvement characterized by proximal tubular damage, which slowly improved but still persisted at the 8-month follow-up. The pathogenesis of the damage is unclear and probably multifactorial.
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The development of smart nanoparticles (NPs) that encode responsive features in the structural framework promises to extend the applications of NP-based drugs, vaccines, and diagnostic tools. New nanocarriers would ideally consist of a minimal number of biocompatible components and exhibit multiresponsive behavior to specific biomolecules, but progress is limited by the difficulty of synthesizing suitable building blocks. Through a nature-inspired approach that combines the programmability of nucleic acid interactions and sol-gel chemistry, we report the incorporation of synthetic nucleic acids and analogs, as constitutive components, into organosilica NPs. We prepared different nanomaterials containing single-stranded nucleic acids that are covalently embedded in the silica network. Through the incorporation of functional nucleic acids into the organosilica framework, the particles respond to various biological, physical, and chemical inputs, resulting in detectable physicochemical changes. The one-step bottom-up approach used to prepare organosilica NPs provides multifunctional systems that combine the tunability of oligonucleotides with the stiffness, low cost, and biocompatibility of silica for different applications ranging from drug delivery to sensing.
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Nanopartículas , Ácidos Nucleicos , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química , Dióxido de Silicio/químicaRESUMEN
One of the most appealing approaches for regulating gene expression, named the "microRNA therapeutic" method, is based on the regulation of the activity of microRNAs (miRNAs), the intracellular levels of which are dysregulated in many diseases, including cancer. This can be achieved by miRNA inhibition with antimiRNA molecules in the case of overexpressed microRNAs, or by using miRNA-mimics to restore downregulated microRNAs that are associated with the target disease. The development of new efficient, low-toxic, and targeted vectors of such molecules represents a key topic in the field of the pharmacological modulation of microRNAs. We compared the delivery efficiency of a small library of cationic calix[4]arene vectors complexed with fluorescent antimiRNA molecules (Peptide Nucleic Acids, PNAs), pre-miRNA (microRNA precursors), and mature microRNAs, in glioma- and colon-cancer cellular models. The transfection was assayed by cytofluorimetry, cell imaging assays, and RT-qPCR. The calix[4]arene-based vectors were shown to be powerful tools to facilitate the uptake of both neutral (PNAs) and negatively charged (pre-miRNAs and mature microRNAs) molecules showing low toxicity in transfected cells and ability to compete with commercially available vectors in terms of delivery efficiency. These results could be of great interest to validate microRNA therapeutics approaches for future application in personalized treatment and precision medicine.