Induced pluripotent stem (iPS) cell research has been growing a new height throughout the world due to its potentialities in medical applications. We can explore several therapeutic applications through the iPS cell research. In this review, we have first discussed the development of iPS cells, reprogramming factors, and effectiveness of iPS cells. Then we have emphasized the potential applications of iPS cells in pharmaceutical and medical sectors, such as, study of cellular mechanisms for spectrum of disease entities, disease-specific iPS cell lines for drugs discovery and development, toxicological studies of drugs development, personalized medicine, and regenerative medicine. Keywords: Induced pluripotent stem (iPS) cell, disease-specific iPS cell lines, drug discovery and development, toxicological studies, personalized medicine, regenerative medicine, Yamanaka Factors, blastomeres, HMG-box, histone acetyltransferases, c-Myc, Nanog, pluripotency, retrovirus, lentivirus, doxycycline, keratinocytes, neurodegenerative disorders, amyotrophic lateral sclerosis, spinal muscular atrophy, Huntington's disease, Alzheimer's disease, Parkinson's disease, Anderson-Fabry disease, transplantation
In the past few years, therapeutic microRNA (miRNA) and small interfering RNA (siRNA) are some of the most important biopharmaceuticals that are in commercial space as future medicines. This review summarizes the patents of miRNA- and siRNA-based new drugs, and also provides a snapshot about significant biopharmaceutical companies that are investing for the therapeutic development of miRNA and siRNA molecules. An insightful view about individual siRNA and miRNA drugs has been depicted with their present status, which is gaining attention in the therapeutic landscape. The efforts of the biopharmaceuticals are discussed with the status of their preclinical and/or clinical trials. Here, some of the setbacks have been highlighted during the biopharmaceutical development of miRNA and siRNA as individual therapeutics. Finally, a snapshot is illustrated about pharmacokinetics, pharmacodynamics with absorption, distribution, metabolism, and excretion (ADME), which is the fundamental development process of these therapeutics, as well as the delivery system for miRNA- and siRNA-based drugs.
Effective cancer management depends on early diagnosis and treatment. There are several microRNAs (miRNAs) which are used for detection of various cancers. Cell-free and circulating miRNAs originate from plasma, either from blood cells or endothelial cells. Cell-free and circulating miRNAs are very much important in the diagnosis and prognosis of cancer therapy. Admittedly, biological knowledge of extracellular miRNAs is still at its preliminary level. Recent discoveries of novel cell-free and circulating miRNAs from the body fluids are now being considered as important biomarkers that may help us in the early diagnosis of any cancer. In the present review, we highlight the biogenesis of miRNAs and their current extracellular pattern, the discovery of circulating miRNA, significant advantages, and different profiling techniques. Finally, we discuss the different circulating miRNAs such as miR-21, miR-20a, miR-155, miR‑221, miR-210, miR-218, miR-200-family, miR-141, miR-122, miR-486-5p, miR‑423-5p, miR-29a, and miR-500 for clinical diagnosis of various cancers. The present review may be beneficial for future researches concerned with miRNAs which are used for detection of various cancers.
Dear Editor, The monkeypox virus (MPXV) continues to spread across different countries in the world. The disease caused by MPXV is an uncommon viral zoonotic disease that is occasionally considered life-threatening. Earlier, the monkeypox disease was epidemic to the African countries, and it spread later to various populations and numbers of geographical areas of non-African countries. Genomic instability and mutational changes also become the significant factors for the re-emergence of human MPXV, animals (non-human) to human, and human to human transmission [1,2]. Several countries (e.g. USA, UK, Canada) have initiated a “ring vaccination” strategy to resist the spread of MPXV, which is a selective vaccination approach that successfully contained smallpox and Ebola outbreaks. The Centers for Disease Control and Prevention (CDC) advises people who are considered at high risk for MPXV infection to get vaccinated against the virus [3]. But precisely, the vaccine candidate has not been developed specifically against MPXV, and therefore smallpox vaccines are recommended assuming to be 85% effective by providing cross-protective immunity against the MPXV infection, as per WHO and CDC. However, smallpox vaccines have minimal testing against MPXV infection, and this assessment was based on the past data from the infection in the African region, where the MPXV outbreaks occurred decades ago [4]. Currently, some vaccines being used against smallpox infection have also been applied to prevent MPXV infection in humans (Table 1) [5]. Out of these vaccines, two vaccines were licensed for use against infection in the USA, JYNNEOS (known as Imvanex or Imvamune) and ACAM200 [6]. The JYNNEOS is a live non-replicating virus vaccine, which is given as two injections within four weeks [7], while the ACAM2000 vaccine is given as a live virus preparation by pricking the skin surface that grows at the lesion site and might spread to other parts of the body or other people. Having questions about the side effects of MPX vaccines is reasonable. The JYNNEOS vaccine has few side effects after vaccination, such as headache, fatigue, nausea, pain at the injection spot, swelling, and redness visible at the injection site within the first couple of days after vaccination [5]. In the ACAM2000 vaccination, individuals suffered fever, small rash, lymph node swelling, and other associated adverse complications (myocarditis and pericarditis) along with pain, swelling, and redness. This vaccine is unsafe and risky for pregnant women, infants, immunocompromised, or individuals living with HIV [8]. The JYNNEOS vaccine is considered to be less reactogenic rather than other traditional smallpox vaccines. Another specialized vaccine known as Aventis Pasteur Smallpox Vaccine (APSV) is presently being offered to humans in a few countries (UK, Spain) [9].Table 1: Smallpox vaccines and their status, used against the MPXV infection.Of note, a specialized next-generation vaccine can be developed based on the genomic sequence information of MPXV. The essential viral protein(s) is considered as vaccine antigens and used as the coding sequence for vaccine development. This peptide-based vaccine formulation platform is highly acceptable rather the conventional procedure of vaccine development. It should have higher efficiency, be less expensive, and speed up the process of covering different mutational variants of this virus [10]. Most nucleic acid-based vaccines, such as DNA and mRNA, can quickly be adapted in case of a newly emerging virus involving a next-generation vaccine development platform. Next-generation vaccine should be the most reliable vaccine platform for manufacturing vaccine candidates in a faster way when a new pathogenic virus emerges shortly and acquire mutations. If we look at the evolution of the MPXV, the virus separated from Orthopoxviruses approximately 3500 years ago through the continuous evolution derived from the mutation. It has been observed that undergoing the evolution process, and the genetic variation produced the MPXV West African subtype about 600 years ago. Researchers have also informed about two initial clades of the African MPXV, which are i) CB Clade or the Congo Basin Clade (Clade I). It originated in the Central part of Africa ii) WA Clade or West African Clade, the second one from the West African (WA) Clade (Clade II). WA Clade or Clade II has been further divided into Clade IIa and Clade IIb. Nakazawa et al. have highlighted that the branches of the CB clade are much shorter. The researchers indicated a recent diversification within this clade; they have described the biogeographic barriers accountable for the CB-WA split [11]. We have recently developed the phylogenomic illustration of the current MPXV and the mutational landscape [1]. Some other researchers have demonstrated phylogenomic illustration or molecular evolution of the current MPXV [12–14]. At the same time, researchers illustrated two important directions: one, mutation and phylogenetics; second, mutation and pathogenicity [12]. Researchers have found 24 non-synonymous variations. Among them, some mutations such as M1741I, P722S, and D209N, located in B21R surface glycoprotein, are associated with the immune evasion process and enhance transmissibility of the MPXV [15]. Several other researchers found the elevated frequency of TC→TT and GA→AA in the genome sequences [1,15]. However, a continuous mutation is found in the MPXV, which demands a mutation-proof vaccine for the MPXV. Recently, we have already urged for a mutation-proof vaccine for SARS-CoV-2 considering mutations [16]. The mutation-proof vaccine might be more effective against a mutating pathogen including the MPXV. In this case, mutations are considered during the coding sequence selection for vaccine development. The vaccine candidate should be effective, safe, and unable to induce the enriched diseases following infection. Subsequently, large-scale production can be done quickly, increasing the flexibility of vaccines to antigenic changes in circulating strains. Developing next-generation vaccine against MPX is crucial to define our real expectations from this vaccine or the need for the future emerging mutational variants of MPXV. The current outbreak of MPXV does have certain unfamiliar features, containing the persistent patterns of human-to-human transmission when men have sex with men. Therefore, the human MPXV is no longer considered a sporadic zoonotic disease, and its rapid spread in more than 100 countries has posed high global public health concerns [17]. It also requires more study to know whether any new transmission pattern has emerged or not [18]. We already know about the pandemic periods of SARS-CoV-2 infection, and the virus quickly emerged to become a critical human pathogen causing the ongoing COVID-19 pandemic. The COVID-19 pandemic phases with multiple waves repeatedly faced surge in cases, high mortality, severe infections, breakthrough vaccine infections and reinfection owing to continuously emerging SARS-CoV-2 mutants, variants and lineages possessing higher transmissibility and severe disease causing ability via overpowering protection levels of vaccine induced immunity and antibodies-based therapies through immune escape mechanisms. So, it seems to be proactive to prepare effective and advanced next generation vaccines against any pathogenic viruses or microbes, although they presently may not be showing higher death cases as a major threat. For MPXV, existing vaccines and drugs still have certain shortcomings. Clinical trials have not confirmed the vaccines' efficacy and safety profile and larger trials are required for assessing smallpox vaccine efficacy against MPX. In this respect, high-end research in advanced platforms is urgently needed to develop suitable next-generation vaccines against MPXV for countering its currently emerging and future threats. Ethical approval No applicable. Sources of funding No fund received. Author contribution Manojit Bhattacharya: Data Curation, Investigation, Writing - Original Draft. Kuldeep Dhama: Validation; editing-reviewing. Chiranjib Chakraborty: Conceptualization, Investigation, Writing - Original Draft, Writing - review & editing. All authors critically reviewed and approved the final version of the manuscript. Conflicts of interest All authors report no conflicts of interest relevant to this article. Registration of research studies Name of the registry: Not applicable Unique Identifying number or registration ID: Not applicable Hyperlink to your specific registration (must be publicly accessible and will be checked): Not applicable Guarantor Professor Chiranjib Chakraborty. Department of Biotechnology, School of Life Science and Biotechnology. Adamas University, Kolkata, West Bengal 700,126, India. Email: [email protected] Tel: +91-9871608125. Consent Not applicable. Provenance and peer review Not commissioned, internally peer-reviewed. Data statement The data in this correspondence article is not sensitive in nature and is accessible in the public domain. The data is therefore available and not of a confidential nature. Acknowledgements All authors are thankful to their respective institutes and universities. Manojit Bhattacharya Kuldeep Dhama Chiranjib Chakraborty 1Department of Zoology, Fakir Mohan University, Vyasa Vihar, Balasore, 756020, Odisha, India 2Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, 243122, Uttar Pradesh, India 3Department of Biotechnology, School of Life Science and Biotechnology, Adamas University, Kolkata, West Bengal, 700126, India E-mail addresses:[email protected]; [email protected]; [email protected]
Abstract Recent efforts in designing nanomaterials to deliver potential therapeutics to the targeted site are overwhelming and palpable. Engineering nanomaterials to deliver biological molecules to exert desirable physiological changes, with minimized side effects and optimal dose, has revolutionized the next-generation therapy for several diseases. The rapid progress of nucleic acids as biopharmaceutics is going to alter the traditional pharmaceutics practices in modern medicine. However, enzymatic instability, large size, dense negative charge (hydrophilic for cell uptake), and unintentional adverse biological responses—such as prolongation of the blood coagulation and immune system activation—hamper the potential use of nucleic acids for therapeutic purposes. Moreover, the safe delivery of nucleic acids into the clinical setting is an uphill task, and several efforts are being put forward to deliver them to targeted cells. Advances in Metal-based NanoParticles (MNPs) are drawing attention due to the unique properties offered by them for drug delivery, such as large surface-area-to-volume ratio for surface modification, increased therapeutic index of drugs through site-specific delivery, increased stability, enhanced half-life of the drug in circulation, and efficient biodistribution to the desired targeted site. Here, the potential of nanoparticles delivery systems for the delivery of nucleic acids, specially MNPs, and their ability and advantages over other nano delivery systems are reviewed. Graphical Abstract
As the COVID-19 is still growing throughout the globe, a thorough investigation into the specific immunopathology of SARS-CoV-2, its interaction with the host immune system and pathogen evasion mechanism may provide a clear picture of how the pathogen can breach the host immune defenses in elderly patients and patients with comorbid conditions. Such studies will also reveal the underlying mechanism of how children and young patients can withstand the disease better. The study of the immune defense mechanisms and the prolonged immune memory from patients population with convalescent plasma may help in designing a suitable vaccine candidate not only for the current outbreak but also for similar outbreaks in the future. The vital drug candidates, which are being tested as potential vaccines or therapeutics against COVID-19, include live attenuated vaccine, inactivated or killed vaccine, subunit vaccine, antibodies, interferon treatment, repurposing existing drugs, and nucleic acid-based vaccines. Several organizations around the world have fast-tracked the development of a COVID-19 vaccine, and some drugs already went to phase III of clinical trials. Hence, here, we have tried to take a quick glimpse of the development stages of vaccines or therapeutic approaches to treat this deadly disease.