Single-domain antibodies and aptamers drive new opportunities for neurodegenerative disease research.

Neurodegenerative diseases (NDs) in mammals, such as Alzheimer's disease (AD), Parkinson's disease (PD), and transmissible spongiform encephalopathies (TSEs), are characterized by the accumulation of misfolded proteins in the central nervous system (CNS). Despite the presence of these pathogenic proteins, the immune response in affected individuals remains notably muted. Traditional immunological strategies, particularly those reliant on monoclonal antibodies (mAbs), face challenges related to tissue penetration, blood-brain barrier (BBB) crossing, and maintaining protein stability. This has led to a burgeoning interest in alternative immunotherapeutic avenues. Notably, single-domain antibodies (or nanobodies) and aptamers have emerged as promising candidates, as their reduced size facilitates high affinity antigen binding and they exhibit superior biophysical stability compared to mAbs. Aptamers, synthetic molecules generated from DNA or RNA ligands, present both rapid production times and cost-effective solutions. Both nanobodies and aptamers exhibit inherent qualities suitable for ND research and therapeutic development. Cross-seeding events must be considered in both traditional and small-molecule-based immunodiagnostic and therapeutic approaches, as well as subsequent neurotoxic impacts and complications beyond protein aggregates. This review delineates the challenges traditional immunological methods pose in ND research and underscores the potential of nanobodies and aptamers in advancing next-generation ND diagnostics and therapeutics.

Combination of locoregional radiotherapy with a TIM-3 aptamer improves survival in diffuse midline glioma models.

Pediatric diffuse midline gliomas (DMG) with altered H3-K27M are aggressive brain tumors that arise during childhood. Despite advances in genomic knowledge and the significant number of clinical trials testing new targeted therapies, patient outcomes are still poor. Immune checkpoint blockades with small molecules, such as aptamers, are opening new therapeutic options that represent hope for this orphan disease. Here, we demonstrated that a TIM-3 aptamer (TIM-3 Apt) as monotherapy increased the immune infiltration and elicited a strong specific immune response with a tendency to improve the overall survival of treated DMG-bearing mice. Importantly, combining TIM-3 Apt with radiotherapy increased the overall median survival and led to long-term survivor mice in 2 pediatric DMG orthotopic murine models. Interestingly, TIM-3 Apt administration increased the number of myeloid populations and the proinflammatory CD8-to-Tregs ratios in the tumor microenvironment as compared with nontreated groups after radiotherapy. Importantly, the depletion of T cells led to a major loss of the therapeutic effect achieved by the combination. This work uncovers TIM-3 targeting as an immunotherapy approach to improve the radiotherapy outcome in DMGs and offers a strong foundation for propelling a phase I clinical trial using radiotherapy and TIM-3 blockade combination as a treatment for these tumors.

Aptamer-functionalized triptolide with release controllability as a promising targeted therapy against triple-negative breast cancer.

Targeted delivery and precise release of toxins is a prospective strategy for the treatment of triple-negative breast cancer (TNBC), yet the flexibility to incorporate both properties simultaneously remains tremendously challenging in the X-drug conjugate fields. As critical components in conjugates, linkers could flourish in achieving optimal functionalities. Here, we pioneered a pH-hypersensitive tumor-targeting aptamer AS1411-triptolide conjugate (AS-TP) to achieve smart release of the toxin and targeted therapy against TNBC. The multifunctional acetal ester linker in the AS-TP site-specifically blocked triptolide toxicity, quantitatively sustained aptamer targeting, and ensured the circulating stability. Furthermore, the aptamer modification endowed triptolide with favorable water solubility and bioavailability and facilitated endocytosis of conjugated triptolide by TNBC cells in a nucleolin-dependent manner. The integrated superiorities of AS-TP promoted the preferential intra-tumor triptolide accumulation in xenografted TNBC mice and triggered the in-situ triptolide release in the weakly acidic tumor microenvironment, manifesting striking anti-TNBC efficacy and virtually eliminated toxic effects beyond clinical drugs. This study illustrated the therapeutic potential of AS-TP against TNBC and proposed a promising concept for the development of nucleic acid-based targeted anticancer drugs.

Aptamer Proteomics for Biomarker Discovery in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Proteomic Substudy.

BACKGROUND: Prognostic markers and biological pathways linked to detrimental clinical outcomes in heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. METHODS AND RESULTS: We measured serum levels of 4123 unique proteins in 1117 patients with HFpEF enrolled in the PARAGON-HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) trial using a modified aptamer proteomic assay. Baseline circulating protein concentrations significantly associated with the primary end point and the timing and occurrence of total heart failure hospitalization and cardiovascular death were identified by recurrent events regression, accounting for multiple testing, adjusted for age, sex, treatment, and anticoagulant use, and compared with published analyses in 2515 patients with heart failure with reduced ejection fraction from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and ATMOSPHERE (Efficacy and Safety of Aliskiren and Aliskiren/Enalapril Combination on Morbidity-Mortality in Patients With Chronic Heart Failure) clinical trials. We identified 288 proteins that were robustly associated with the risk of heart failure hospitalization and cardiovascular death in patients with HFpEF. The baseline proteins most strongly related to outcomes included B2M (ß-2 microglobulin), TIMP1 (tissue inhibitor of matrix metalloproteinase 1), SERPINA4 (serpin family A member 4), and SVEP1 (sushi, von Willebrand factor type A, EGF, and pentraxin domain containing 1). Overall, the protein-outcome associations in patients with HFpEF did not markedly differ as compared with patients with heart failure with reduced ejection fraction. A proteomic risk score derived in patients with HFpEF was not superior to a previous proteomic score derived in heart failure with reduced ejection fraction nor to clinical risk factors, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or high-sensitivity cardiac troponin. CONCLUSIONS: Numerous serum proteins linked to metabolic, coagulation, and extracellular matrix regulatory pathways were associated with worse HFpEF prognosis in the PARAGON-HF proteomic substudy. Our results demonstrate substantial similarities among serum proteomic risk markers for heart failure hospitalization and cardiovascular death when comparing clinical trial participants with heart failure across the ejection fraction spectrum. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifiers: NCT01920711, NCT01035255, NCT00853658.

Aptamers: ushering in new hopes in targeted glioblastoma therapy.

Glioblastoma, a formidable brain cancer, has remained a therapeutic challenge due to its aggressive nature and resistance to conventional treatments. Recent data indicate that aptamers, short synthetic DNA or RNA molecules can be used in anti-cancer therapy due to their better tumour penetration, specific binding affinity, longer retention in tumour sites and their ability to cross the blood-brain barrier. With the ability to modify these oligonucleotides through the selection process, and using rational design to modify them, post-SELEX aptamers offer several advantages in glioblastoma treatment, including precise targeting of cancer cells while sparing healthy tissue. This review discusses the pivotal role of aptamers in glioblastoma therapy and diagnosis, emphasising their potential to enhance treatment efficacy and also highlights recent advancements in aptamer-based therapies which can transform the landscape of glioblastoma treatment, offering renewed hope to patients and clinicians alike.

Breaking Barriers: Nucleic Acid Aptamers in Gastrointestinal (GI) Cancers Therapy.

Conventional cancer therapies can have significant adverse effects as they are not targeted to cancer cells and may damage healthy cells. Single-stranded oligonucleotides assembled in a particular architecture, known as aptamers, enable them to attach selectively to target areas. Usually, they are created by Systematic Evolution of Ligand by Exponential enrichment (SELEX), and they go through a rigorous pharmacological revision process to change their therapeutic half-life, affinity, and specificity. They could thus offer a viable substitute for antibodies in the targeted cancer treatment market. Although aptamers can be a better choice in some situations, antibodies are still appropriate for many other uses. The technique of delivering aptamers is simple and reasonable, and the time needed to manufacture them is relatively brief. Aptamers do not require animals or an immune response to be produced, in contrast to antibodies. When used as a medication, aptamers can directly suppress tumor cells. As an alternative, they can be included in systems for targeted drug delivery that administer medications specifically to tumor cells while reducing toxicity to healthy cells. The most recent and cutting-edge methods for treating gastrointestinal (GI) tract cancer with aptamers will be covered in this review, with a focus on targeted therapy as a means of conquering resistance to traditional medicines.

Anti-vascular endothelial growth factor biosimilars for neovascular age-related macular degeneration.

RATIONALE: Neovascular age-related macular degeneration (AMD) is a progressive eye disease characterized by choroidal neovascularization (CNV) and is a leading cause of vision loss and disability worldwide. Although intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is an effective treatment option that helps to prevent vision loss or to improve visual acuity in people with neovascular AMD, treatment imposes a significant financial burden on patients and healthcare systems. A biosimilar is a biological product that has been developed to be nearly identical to a previously approved biological product. The use of biosimilars may help reduce costs and so may increase patient access to effective biologic medicines with similar levels of safety to the drugs on which they are based. OBJECTIVES: To assess the benefits and harms of anti-VEGF biosimilar agents compared with their corresponding anti-VEGF agents (i.e. the reference products) that have obtained regulatory approval for intravitreal injections in people with neovascular AMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two other databases, and two trials registries together with reference checking and contact with study authors to identify studies that are included in the review. The latest search date was 2 June 2023. ELIGIBILITY CRITERIA: We included randomized controlled trials (RCTs) that compared approved anti-VEGF biosimilars with their reference products for treating the eyes of adult participants (≥ 50 years) who had an active primary or recurrent choroidal neovascularization lesion secondary to neovascular AMD. OUTCOMES: Our outcomes were: best-corrected visual acuity (BCVA), central subfield thickness (CST), vision-related quality of life, serious ocular and non-ocular adverse events (AE), treatment-emergent adverse events (TEAEs), anti-drug antibodies (ADAs), and serum concentrations of biosimilars and reference drugs. RISK OF BIAS: We assessed the risk of bias (RoB) for seven outcomes reported in a summary of findings table by using the Cochrane RoB 2 tool. SYNTHESIS METHODS: We synthesized results for each outcome using meta-analysis, where possible, by calculating risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for dichotomous outcomes and continuous outcomes, respectively. Where this was not possible due to the nature of the data, we summarized the results narratively. We used GRADE to assess the certainty of evidence for prespecified outcomes. INCLUDED STUDIES: We included nine parallel-group multi-center RCTs that enrolled a total of 3814 participants (3814 participating eyes), with sample sizes that ranged from 160 to 705 participants per study. The mean age of the participants in these studies ranged from 67 to 76 years, and the proportion of women ranged from 26.5% to 58.7%. Ranibizumab (Lucentis) was the reference product in seven studies, and aflibercept (Eyelea) was the reference product in two others. All the included studies had been supported by industry. The follow-up periods ranged from 12 to 52 weeks (median 48 weeks). Five studies (56%) were conducted in multi-country settings across Europe, North America and Asia, two studies in India, and one each in Japan and the Republic of Korea. We judged all the included studies to have met high methodological standards. SYNTHESIS OF RESULTS: With regard to efficacy, our meta-analyses demonstrated that anti-VEGF biosimilars for neovascular AMD resulted in little to no difference compared with the reference products for BCVA change at 8 to 12 weeks (MD -0.55 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, 95% CI -1.17 to 0.07; 8 studies, 3603 participants; high-certainty evidence) and the proportion of participants who lost fewer than 15 letters in BCVA at 24 to 48 weeks (RR 0.99, 95% CI 0.98 to 1.01; 7 studies, 2658 participants; moderate-certainty evidence). Almost all participants (96.6% in the biosimilar group and 97.0% in the reference product group) lost fewer than 15 letters in BCVA. The evidence from two studies suggested that there was no evidence of difference between biosimilars and reference products in vision-related quality of life measured by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) summary scores at 24 to 48 weeks (MD 0.82, 95% CI -0.70 to 2.35; 2 studies, 894 participants; moderate-certainty evidence). With regard to the safety profile, meta-analyses also revealed little to no difference between anti-VEGF biosimilars and the reference products for the proportion of participants who experienced serious ocular AEs (RR 1.24, 95% CI 0.68 to 2.26; 7 studies, 3292 participants; moderate-certainty evidence), and for TEAEs leading to investigational product discontinuation or death (RR 0.96, 95% CI 0.63 to 1.46; 8 studies, 3497 participants; moderate-certainty evidence). Overall, 1.4% of participants in the biosimilar group and 1.2% in the reference product group experienced serious ocular adverse events. The most frequently documented serious ocular AEs were retinal hemorrhage and endophthalmitis. Although the evidence is of low certainty due to imprecision, meta-analysis suggested that anti-VEGF biosimilars led to no difference compared with the reference products for cumulative incidence of ADAs (RR 0.84, 95% CI 0.58 to 1.22; 8 studies, 3066 participants; low-certainty evidence) or mean maximum serum concentrations (MD 0.42 ng/mL, 95% CI -0.22 to 1.05; subgroup of 3 studies, 100 participants; low-certainty evidence). We judged the overall risk of bias to be low for all studies. AUTHORS' CONCLUSIONS: In our review, low to high certainty evidence suggests that there is little to no difference, to date, between the anti-VEGF biosimilars approved for treating neovascular AMD and their reference products in terms of benefits and harms. While anti-VEGF biosimilars may be a viable alternative to reference products, current evidence for their use is based on a limited number of studies - particularly for comparison with aflibercept - with sparse long-term safety data, and infrequent assessment of quality of life outcomes. Our effect estimates and conclusions may be modified once findings have been reported from studies that are currently ongoing, and studies of biosimilar agents that are currently in development. FUNDING: Cochrane Eyes and Vision US Project is supported by grant UG1EY020522, National Eye Institute, National Institutes of Health. Takeshi Hasegawa and Hisashi Noma were supported by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Grant numbers: 22H03554, 19K03092, 24K06239). REGISTRATION: Protocol available via doi.org/10.1002/14651858.CD015804.

Role of aptamer technology in extracellular vesicle biology and therapeutic applications.

Extracellular vesicles (EVs) are cell-derived nanosized membrane-bound vesicles that are important intercellular signalling regulators in local cell-to-cell and distant cell-to-tissue communication. Their inherent capacity to transverse cell membranes and transfer complex bioactive cargo reflective of their cell source, as well as their ability to be modified through various engineering and modification strategies, have attracted significant therapeutic interest. Molecular bioengineering strategies are providing a new frontier for EV-based therapy, including novel mRNA vaccines, antigen cross-presentation and immunotherapy, organ delivery and repair, and cancer immune surveillance and targeted therapeutics. The revolution of EVs, their diversity as biocarriers and their potential to contribute to intercellular communication, is well understood and appreciated but is ultimately dependent on the development of methods and techniques for their isolation, characterization and enhanced targeting. As single-stranded oligonucleotides, aptamers, also known as chemical antibodies, offer significant biological, chemical, economic, and therapeutic advantages in terms of their size, selectivity, versatility, and multifunctional programming. Their integration into the field of EVs has been contributing to the development of isolation, detection, and analysis pipelines associated with bioengineering strategies for nano-meets-molecular biology, thus translating their use for therapeutic and diagnostic utility.

Therapeutic Applications of Aptamers.

Affinity reagents, or target-binding molecules, are quite versatile and are major workhorses in molecular biology and medicine. Antibodies are the most famous and frequently used type and they have been used for a wide range of applications, including laboratory techniques, diagnostics, and therapeutics. However, antibodies are not the only available affinity reagents and they do have significant drawbacks, including laborious and costly production. Aptamers are one potential alternative that have a variety of unique advantages. They are single stranded DNA or RNA molecules that can be selected for binding to many targets including proteins, carbohydrates, and small molecules-for which antibodies typically have low affinity. There are also a variety of cost-effective methods for producing and modifying nucleic acids in vitro without cells, whereas antibodies typically require cells or even whole animals. While there are also significant drawbacks to using aptamers in therapeutic applications, including low in vivo stability, aptamers have had success in clinical trials for treating a variety of diseases and two aptamer-based drugs have gained FDA approval. Aptamer development is still ongoing, which could lead to additional applications of aptamer therapeutics, including antitoxins, and combinatorial approaches with nanoparticles and other nucleic acid therapeutics that could improve efficacy.

Aptamer-mediated therapeutic strategies provide a potential approach for cancer.

The treatment of tumors still faces considerable challenges. While conventional treatments such as surgery, chemotherapy, and radiation therapy provide some curative effects, their side effects and limitations highlight the importance of finding more precise treatment strategies. Aptamers have become an important target molecule in the field of drug delivery systems due to their good affinity and targeting, and they have gradually become an important link from basic research to clinical application. In this paper, we discussed the latest progress of aptamer-mediated nanodrugs, as well as aptamer-mediated photodynamic therapy, photothermal therapy, and immunotherapy strategies for tumor treatment, and explored the possibility of aptamer-mediated therapy for accurate tumor treatment. The purpose of this review is to provide novel insights for treating tumors with aptamer-mediated therapies by summarizing these innovative strategies, thereby ultimately enhancing the therapeutic efficacy for cancer patients.

Cost-Effectiveness of Technologies for the Treatment of Spinal Muscular Atrophy: A Systematic Review of Economic Studies.

OBJECTIVES: This study aims to systematically collect data on cost-effectiveness analyses that assess technologies to treat type I and II spinal muscular atrophy and evaluate their recommendations. METHODS: A structured electronic search was conducted in 4 databases. Additionally, a complementary manual search was conducted. Complete economic studies that evaluated nusinersen, risdiplam, onasemnogene abeparvovec (OA), and the best support therapy (BST) from the health system's perspective were selected. The incremental cost-effectiveness ratios were compared with various thresholds for the analysis. The review was registered a priori in PROSPERO (CRD42022365391). RESULTS: Twenty studies were included in the analyses. They were all published between 2017 and 2022 and represent the recommendations in 8 countries. Most studies adopted 5, 6, or 10-state Markov models. Some authors took part in multiple studies. Four technologies were evaluated: BST (N = 14), nusinersen (N = 19), risdiplam (N = 5), and OA (N = 9). OA, risdiplam, and nusinersen were considered inefficient compared with the BST. Risdiplam and OA were generally regarded as cost-effective when compared with nusinersen. Because nusinersen is not a cost-effective drug, no recommendation can be derived from this result. Risdiplam and OA were compared in 2 studies that presented opposite results. CONCLUSIONS: Nusinersen, risdiplam, and OA are being adopted worldwide as a treatment for spinal muscular atrophy. Despite that, the pharmacoeconomic analyses show that the technologies are not cost-effective compared with the BST. The lack of controlled studies for risdiplam and OA hamper any conclusions about their face-to-face comparison.

Aptamers: Promising Reagents in Biomedicine Application.

Nucleic acid aptamers, often termed "chemical antibodies," are short, single-stranded DNA or RNA molecules, which are selected by SELEX. In addition to their high specificity and affinity comparable to traditional antibodies, aptamers have numerous unique advantages such as wider identification of targets, none or low batch-to-batch variations, versatile chemical modifications, rapid mass production, and lack of immunogenicity. These characteristics make aptamers a promising recognition probe for scientific research or even clinical application. Aptamer-functionalized nanomaterials are now emerged as a promising drug delivery system for various diseases with decreased side-effects and improved efficacy. In this review, the technological strategies for generating high-affinity and biostable aptamers are introduced. Moreover, the development of aptamers for their application in biomedicine including aptamer-based biosensors, aptamer-drug conjugates and aptamer functionalized nanomaterials is comprehensively summarized.

Aptamer-Based Targeting of Cancer: A Powerful Tool for Diagnostic and Therapeutic Aims.

Cancer is known as one of the most significant causes of death worldwide, and, in spite of novel therapeutic methods, continues to cause a considerable number of deaths. Targeted molecular diagnosis and therapy using aptamers with high affinity have become popular techniques for pathological angiogenesis and cancer therapy scientists. In this paper, several aptamer-based diagnostic and therapeutic techniques such as aptamer-nanomaterial conjugation, aptamer-drug conjugation (physically or covalently), and biosensors, which have been successfully designed for biomarkers, were critically reviewed. The results demonstrated that aptamers can potentially be incorporated with targeted delivery systems and biosensors for the detection of biomarkers expressed by cancer cells. Aptamer-based therapeutic and diagnostic methods, representing the main field of medical sciences, possess high potential for use in cancer therapy, pathological angiogenesis, and improvement of community health. The clinical use of aptamers is limited due to target impurities, inaccuracy in the systematic evolution of ligands via exponential enrichment (SELEX)stage process, and in vitro synthesis, making them unreliable and leading to lower selectivity for in vivo targets. Moreover, size, behavior, probable toxicity, low distribution, and the unpredictable behavior of nanomaterials in in vivo media make their usage in clinical assays critical. This review is helpful for the implementation of aptamer-based therapies which are effective and applicable for clinical use and the design of future studies.

RNA therapeutics in cancer treatment.

RNA therapeutics are a class of drugs that use RNA molecules to treat diseases, including cancer. RNA therapeutics work by targeting specific genes or proteins involved in the disease process, with the aim of blocking or altering their activity to ultimately halt or reverse the disease progression. The use of RNA therapeutics in cancer treatment has shown great potential, as they offer the ability to specifically target cancer cells while leaving healthy cells intact. This is in contrast to traditional chemotherapy and radiation treatments, which can damage healthy cells and cause unpleasant side effects. The field of RNA therapeutics is rapidly advancing, with several types of RNA molecules being developed for cancer treatment, including small interfering RNA, microRNA, mRNA, and RNA aptamers. Each type of RNA molecule has unique properties and mechanisms of action, allowing for targeted and personalized cancer treatments. In this chapter, we will explore the different types of RNA therapeutics used in cancer treatment, their mechanisms of action, and their potential applications in treating different types of cancer. We will also discuss the challenges and opportunities in the development and research of RNA therapeutics for cancer, as well as the future outlook for this promising field.

Next-generation therapeutics for rare genetic disorders.

The therapeutic potential of the human genome has been explored through the development of next-generation therapeutics, which have had a high impact on treating genetic disorders. Classical treatments have traditionally focused on common diseases that require repeated treatments. However, with the recent advancements in the development of nucleic acids, utilizing DNA and RNA to modify or correct gene expression in genetic disorders, there has been a paradigm shift in the treatment of rare diseases, offering more potential one-time cure options. Advanced technologies that use CRISPR-Cas 9, antisense oligonucleotides, siRNA, miRNA, and aptamers are promising tools that have achieved successful breakthroughs in the treatment of various genetic disorders. The advancement in the chemistry of these molecules has improved their efficacy, reduced toxicity, and expanded their clinical use across a wide range of tissues in various categories of human disorders. However, challenges persist regarding the safety and efficacy of these advanced technologies in translating into clinical practice. This review mainly focuses on the potential therapies for rare genetic diseases and considers how next-generation techniques enable drug development to achieve long-lasting curative effects through gene inhibition, replacement, and editing.

Aptamers in neuro-oncology: An emerging therapeutic modality.

Despite recent advances in the understanding of brain tumor pathophysiology, challenges associated with tumor location and characteristics have prevented significant improvement in neuro-oncology therapies. Aptamers are short, single-stranded DNA or RNA oligonucleotides that fold into sequence-specific, 3-dimensional shapes that, like protein antibodies, interact with targeted ligands with high affinity and specificity. Aptamer technology has recently been applied to neuro-oncology as a potential approach to innovative therapy. Preclinical research has demonstrated the ability of aptamers to overcome some obstacles that have traditionally rendered neuro-oncology therapies ineffective. Potential aptamer advantages include their small size, ability in some cases to penetrate the blood-brain barrier, inherent lack of immunogenicity, and applicability for discovering novel biomarkers. Herein, we review recent reports of aptamer applications in neuro-oncology including aptamers found by cell- and in vivo- Systematic Evolution of Ligands by Exponential Enrichment approaches, aptamer-targeted therapeutic delivery modalities, and aptamers in diagnostics and imaging. We further identify crucial future directions for the field that will be important to advance aptamer-based drugs or tools to clinical application in neuro-oncology.

Advances in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers.

Peptides and peptide aptamers have emerged as promising molecules for a wide range of biomedical applications due to their unique properties and versatile functionalities. The screening strategies for identifying peptides and peptide aptamers with desired properties are discussed, including high-throughput screening, display screening technology, and in silico design approaches. The synthesis methods for the efficient production of peptides and peptide aptamers, such as solid-phase peptide synthesis and biosynthesis technology, are described, along with their advantages and limitations. Moreover, various modification techniques are explored to enhance the stability, specificity, and pharmacokinetic properties of peptides and peptide aptamers. This includes chemical modifications, enzymatic modifications, biomodifications, genetic engineering modifications, and physical modifications. Furthermore, the review highlights the diverse biomedical applications of peptides and peptide aptamers, including targeted drug delivery, diagnostics, and therapeutic. This review provides valuable insights into the advancements in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers. A comprehensive understanding of these aspects will aid researchers in the development of novel peptide-based therapeutics and diagnostic tools for various biomedical challenges.

Aptamer-based diagnostic and therapeutic approaches for animal viruses: A review.

Animal diseases often have significant consequences due to the unclear and time-consuming diagnosis process. Furthermore, the emergence of new viral infections and drug-resistant pathogens has further complicated the diagnosis and treatment of viral diseases. Aptamers, which are obtained through systematic evolution of ligands by exponential enrichment (SELEX) technology, provide a promising solution as they enable specific identification and binding to targets, facilitating pathogen detection and the development of novel therapeutics. This review presented an overview of aptasensors for animal virus detection, discussed the antiviral activity and mechanisms of aptamers, and highlighted advancements in aptamer-based antiviral research following the COVID-19 pandemic. Additionally, the challenges and prospects of aptamer-based virus diagnosis and treatment research were explored. Although this review was not exhaustive, it offered valuable insights into the progress of aptamer-based antiviral drug research, target mechanisms, as well as the development of novel antiviral drugs and biosensors.

Targeting vimentin: a multifaceted approach to combatting cancer metastasis and drug resistance.

This comprehensive review explores vimentin as a pivotal therapeutic target in cancer treatment, with a primary focus on mitigating metastasis and overcoming drug resistance. Vimentin, a key player in cancer progression, is intricately involved in processes such as epithelial-to-mesenchymal transition (EMT) and resistance mechanisms to standard cancer therapies. The review delves into diverse vimentin inhibition strategies. Precision tools, including antibodies and nanobodies, selectively neutralize vimentin's pro-tumorigenic effects. DNA and RNA aptamers disrupt vimentin-associated signaling pathways through their adaptable binding properties. Innovative approaches, such as vimentin-targeted vaccines and microRNAs (miRNAs), harness the immune system and post-transcriptional regulation to combat vimentin-expressing cancer cells. By dissecting vimentin inhibition strategies across these categories, this review provides a comprehensive overview of anti-vimentin therapeutics in cancer treatment. It underscores the growing recognition of vimentin as a pivotal therapeutic target in cancer and presents a diverse array of inhibitors, including antibodies, nanobodies, DNA and RNA aptamers, vaccines, and miRNAs. These multifaceted approaches hold substantial promise for tackling metastasis and overcoming drug resistance, collectively presenting new avenues for enhanced cancer therapy.