Abstract:
:Protein expression therapy using nucleic acid macromolecules (NAMs) as a new paradigm in medicine has recently gained immense therapeutic potential. With the advancement of nonviral delivery it has been possible to target NAMs against cancer, immunodeficiency and infectious diseases. Owing to the complex and fragile structure of NAMs, however, development of a suitable, stable formulation for a reasonable product shelf-life and efficacious delivery is indeed challenging to achieve. This review provides a synopsis of challenges in the formulation and stability of DNA/m-RNA based medicines and probable mitigation strategies including a brief summary of delivery options to the target cells. Nucleic acid based drugs at various stages of ongoing clinical trials are compiled.
journal_name
Drug Discov Todayjournal_title
Drug discovery todayauthors
Muralidhara BK,Baid R,Bishop SM,Huang M,Wang W,Nema Sdoi
10.1016/j.drudis.2015.11.012subject
Has Abstractpub_date
2016-03-01 00:00:00pages
430-44issue
3eissn
1359-6446issn
1878-5832pii
S1359-6446(15)00447-Xjournal_volume
21pub_type
杂志文章,评审abstract::DNA-nanorobot-guided thrombin-inducing tumor infarction (DNA NanorobotTh-ITI) is emerging as a powerful therapeutic strategy for treatment of solid cancers. The technology represents a major advance in the application of DNA nanotechnology for anticancer therapy. More importantly, the technology is being translated fr...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2020.03.005
更新日期:2020-06-01 00:00:00
abstract::Drug delivery systems are undergoing technology changes to enhance patient comfort and compliance. Electronic drug delivery (E-drug delivery) systems are being developed to regulate drug dose delivery by easy monitoring of doses, especially in chronic and age-related diseases. E-drug delivery can monitor the correct d...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.02.005
更新日期:2019-04-01 00:00:00
abstract::Magnetic nanoparticles (MNPs) play a vital role for improved imaging applications. Recently, a number of studies demonstrate MNPs can be applied for targeted delivery, sustained release of therapeutics, and hyperthermia. Based on stable particle size and shape, biocompatibility, and inherent contrast enhancement chara...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.04.018
更新日期:2017-08-01 00:00:00
abstract::Owing to their structural diversity, peptides are a unique source of innovative active ingredients. However, their development has been challenging because of their disadvantageous pharmacokinetic (PK) properties. Over the past decade, many attempts have been made to improve the oral bioavailability of peptide drugs. ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2021.01.020
更新日期:2021-01-23 00:00:00
abstract::Diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) have emerged as effective low-density lipoprotein cholesterol-lowering compounds. Although the results of available epidemiological, preclinical, and clinical...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.01.006
更新日期:2017-06-01 00:00:00
abstract::The prevalence of obesity is increasing at an alarming rate, but, unfortunately, only a few medications are currently on the market. Obesity is primarily regarded as a disorder of lipid metabolism and the enzymes involved in this process could be selectively targeted to develop antiobesity drugs. Recently, newer appro...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2007.07.024
更新日期:2007-10-01 00:00:00
abstract::The occurrence of drug resistance in oncology accounts for treatment failure and relapse of diverse tumor types. Cancers contain cells at various stages of differentiation together with a limited number of 'cancer-initiating cells' able to self-renew and divide asymmetrically, driving tumorigenesis. Cancer-initiating ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2011.02.005
更新日期:2012-05-01 00:00:00
abstract::Tuberculosis drug discovery has shifted in recent years from a primarily target-based approach to one that uses phenotypic high-throughput screens. As examples of this, through our EU-funded FP7 collaborations, New Medicines for Tuberculosis was target-based and our more-recent More Medicines for Tuberculosis project ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.09.025
更新日期:2017-03-01 00:00:00
abstract::Skin is a vital protective organ, the main role of which is to provide a physical barrier and to prevent the entry of pathogens. Various pathologies, such as atopic dermatitis (AD), psoriasis (PSO), or skin cancers, can affect the skin, and all show a high and increasing prevalence. Many antibodies are currently used ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.10.023
更新日期:2021-01-01 00:00:00
abstract::Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevan...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(01)01831-1
更新日期:2001-07-01 00:00:00
abstract::The inhaled delivery of nanomedicines has attracted much attention in the treatment of lung diseases or systemic diseases. However, there is a lack of understanding about their fate upon lung delivery. Thus, the objective of this review is to summarize physicochemical properties affecting the fate of nanoparticles aft...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2019.09.023
更新日期:2020-01-01 00:00:00
abstract::Gene expression microarrays have been used widely to address increasingly complex biological questions and to produce an unprecedented amount of data, but have yet to realize their full potential. The interpretation of microarray data remains a major challenge because of the complexity of the underlying biological net...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03565-8
更新日期:2005-09-01 00:00:00
abstract::When cross-reactivity of a lead antibody across species is limited, antibody development programs require the generation of surrogate molecules or surrogate animal models necessary for the conduct of preclinical pharmacology and safety studies. When surrogate approaches are employed, the complexities and challenges fo...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2009.09.014
更新日期:2009-12-01 00:00:00
abstract::The operational model of agonism assumes that the maximum effect a particular receptor system can achieve (the Em parameter) is fixed. Em estimates are above but close to the asymptotic maximum effects of endogenous agonists. The concept of Em is contradicted by superagonists and those positive allosteric modulators t...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2012.12.004
更新日期:2013-04-01 00:00:00
abstract::Here, I provide an overview of the solid-state characteristics, phase transformations and chemical reactions of metoclopramide hydrochloride monohydrate (MCP HCl H2O). Three unique techniques, including thermoanalytical methods, one-step simultaneous differential scanning calorimetry (DSC) and Fourier transform infrar...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.10.001
更新日期:2015-02-01 00:00:00
abstract::Although the oral route is the most popular and acceptable way of drug administration owing to good patient compliance and safety, oral drug delivery is faced with continuous challenges regarding poorly soluble, poorly permeable or gastrointestinally unstable drugs such as proteins and polypeptides. The overall bioava...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.03.001
更新日期:2014-07-01 00:00:00
abstract::Polymer-drug conjugates (PDC) have exhibited clinical and commercial success in the field of drug delivery. A polymeric backbone, linker, targeting moiety, and drug constitute the building blocks of PDCs. Current attention is focusing on natural polymeric carriers, in particular the concept of graft copolymers, such a...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.06.028
更新日期:2020-09-01 00:00:00
abstract::After the pH dependency of novel pH-dependent ileocolonic drug delivery systems is confirmed in vitro, their performance should be evaluated in human volunteers. ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2020.06.011
更新日期:2020-08-01 00:00:00
abstract::The focus of high-throughput drug discovery has progressed through the genome and the transcriptome and is now moving towards more difficult problems in assessing the proteome, glycome and metabolome. Microarrays are currently the major tool in the assessment of gene expression via cDNA or RNA analysis; however, they ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/s1359-6446(03)02773-9
更新日期:2003-07-15 00:00:00
abstract::A quantitative analysis has cast doubt over the limited advantages provided by particles for nose-to-brain (NTB) drug delivery. Thus, it is imperative to identify the role of nanovehicles in NTB drug delivery. If nanocarriers are used merely as an option to improve various properties of the drugs or the formulations, ...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2018.01.005
更新日期:2018-05-01 00:00:00
abstract::Drugs targeting infectious diseases have greatly improved public health. A study to evaluate all US Food and Drug Administration (FDA)-approved new molecular entities (NMEs) reveals that the number of new agents targeting infectious disease peaked during the 1990s and declined rapidly thereafter. Molecules targeting b...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/j.drudis.2014.07.005
更新日期:2014-09-01 00:00:00
abstract::Stimulation of bone regeneration using growth factors is a promising approach for musculoskeletal regenerative engineering. However, common limitations with protein growth factors, such as high manufacturing costs, protein instability, contamination issues, and unwanted immunogenic responses of the host reduce potenti...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2014.01.012
更新日期:2014-06-01 00:00:00
abstract::In recent years, advances in tissue engineering and microfabrication technologies have enabled rapid growth in the areas of in vitro organoid development as well as organoid-on-a-chip platforms. These 3D model systems often are able to mimic human physiology more accurately than traditional 2D cultures and animal mode...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2016.07.003
更新日期:2016-09-01 00:00:00
abstract::Although many existing methods are used to study the functions of ion channels and to screen lead compounds for important ion-channel targets, new technologies are being developed for improved performance. It is important to identify the advantages and disadvantages of each technology. In this review, we segment the i...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(01)02095-5
更新日期:2001-12-15 00:00:00
abstract::Drug discovery is a time consuming and costly process. Recently, a trend towards the use of in silico computational chemistry and molecular modeling for computer-aided drug design has gained significant momentum. This review investigates the application of free and/or open-source software in the drug discovery process...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(05)03692-5
更新日期:2006-02-01 00:00:00
abstract::The successful cloning and subsequent clinical application of recombinant cytokines and/or growth factors has generated a number of important therapeutics. In contrast to the G-protein-coupled receptors, identification of small-molecule agonists of the cytokine and/or growth factor receptor family has proved difficult...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(00)00062-3
更新日期:2000-12-01 00:00:00
abstract::Translating academic medical research into new therapies is an important challenge for the biopharmaceutical industry and investment communities, which have historically favored later-stage assets with lower risk and clearer commercial value. The Stanford SPARK program is an innovative model for addressing this challe...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2017.03.015
更新日期:2017-07-01 00:00:00
abstract::Peptide-based drugs are now viable alternatives to biopharmaceuticals, such as antibodies. Most of the past limitations of peptides have been removed by new technologies, so that peptides now face similar hurdles to antibodies. Phage-display technology provides novel peptides that bind protein targets with high affini...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/S1359-6446(04)03104-6
更新日期:2004-06-15 00:00:00
abstract::Effective direct inhibition of adhesion receptors by small molecules has been hampered by extended receptor-ligand interfaces as well as the entropic penalties often associated with inhibition of cell adhesion. Therefore, alternative strategies have targeted enzymes that are centrally involved in the biosynthesis of r...
journal_title:Drug discovery today
pub_type: 杂志文章
doi:10.1016/s1359-6446(00)01581-6
更新日期:2001-01-01 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF) is a progressive and almost invariably lethal disease that affects primarily older adults. After a decade of negative (or inconsistent) results, two recent clinical trials have demonstrated that slowing disease progression with medication is possible. An improved understanding of di...
journal_title:Drug discovery today
pub_type: 杂志文章,评审
doi:10.1016/j.drudis.2015.01.001
更新日期:2015-05-01 00:00:00