scholarly journals RNA-targeting Therapy: A Promising Approach to Reach Non-Druggable Targets

2021 ◽  
Vol 14 (4) ◽  
pp. 1781-1790
Author(s):  
Dalia Zaafar ◽  
Toka Elemary ◽  
Yara Abdel Hady ◽  
Aya Essawy

The term "non-druggable" refers to a protein that cannot be targeted pharmacologically; recently, significant efforts have been made to convert these proteins into targets that are reachable or "druggable." Pharmacologically targeting these difficult proteins has emerged as a major challenge in modern drug development, necessitating the innovation and development of new technologies. The idea of using RNA-targeting therapeutics as a platform to reach unreachable targets is very appealing. Antisense oligonucleotides, nucleic acid or aptamers, RNA interference therapeutics, microRNA, and synthetic RNA are examples of RNA-targeting therapeutics. Many of these agents were FDA-approved for the treatment of rare or genetic diseases, as well as molecular markers for disease diagnosis. As a promising type of therapeutic, many studies are being conducted in order for more and more of them to be approved and used in different disease treatments and to shift them from treating rare diseases only to being used as more specific targeting agents in the treatment of various common diseases. This article will look at some of the most recent technological and pharmaceutical advances that have contributed to the erosion of the concept of undruggability.

2021 ◽  
Author(s):  
Daria V. Berdnikova

RNA is an emerging drug target that opens new perspectives in the treatment of viral and bacterial infections, cancer and a range of so far incurable genetic diseases. Among the...


Author(s):  
Niamh Coleman ◽  
Jordi Rodon

The term “undruggable” is used to describe a protein that is not pharmacologically capable of being targeted; recently, however, substantial efforts have been made to turn these proteins into “druggable” targets. Thus, “difficult to drug” or “yet to be drugged” are perhaps more appropriate terms. In cancer, a number of elusive targets fall into this category, including transcription factors such as STAT3, TP53, and MYC. Pharmacologically targeting these intractable proteins is now a key challenge of modern drug development, requiring innovation and the development of new technologies. In this article, we discuss some of the recent technologic and pharmacologic advances that have underpinned the erosion of the concept of undruggability. We describe recent successes in drugging the undruggable RAS ( KRAS G12C and HRAS), and discuss the advances that have led to the validation of further targets previously believed to be undruggable, such as HIF-2α, BCL-2, MDM2, and MLL. Finally, we look to the future and describe important advances that are likely to have a major impact on targeting undruggable targets, such as the advent of proteolysis-targeting chimeras and protein-protein modulators, which are leading to considerable excitement surrounding the development of cancer targets.


1999 ◽  
Vol 25 (4) ◽  
pp. 479-541
Author(s):  
Allyn L. Taylor

The global Human Genome Project (HGP) promises dramatic advances in biomedical science and in identifying and treating diseases and illnesses that exact an enormous toll on people throughout the world. The HGP portends a conceptual revolution in health care: many foresee a new “predictive medicine” based on the development of genetic screening, testing and gene therapy.Although advances in genetic science create the potential for dramatic progress against disease in rich and poor states, they also pose profound national and global policy concerns, including the potential impact of the scientific developments on human rights and public health. The development of more precise genetic information raises the specter of genetic discrimination by public and private sectors in all nations with access to the new technologies. In addition, nations will grapple increasingly with the appropriate balance between screening for and treatment of genetic diseases in order to promote public health and protect individual rights to privacy and confidentiality. Genetic screening and services also raise human rights questions relating to equitable resource allocation and the protection of public health.


Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7063
Author(s):  
Peng Zhang ◽  
Xinyu Ma ◽  
Ruiwei Guo ◽  
Zhanpeng Ye ◽  
Han Fu ◽  
...  

X-ray computed tomography (CT) imaging can produce three-dimensional and high-resolution anatomical images without invasion, which is extremely useful for disease diagnosis in the clinic. However, its applications are still severely limited by the intrinsic drawbacks of contrast media (mainly iodinated water-soluble molecules), such as rapid clearance, serious toxicity, inefficient targetability and poor sensitivity. Due to their high biocompatibility, flexibility in preparation and modification and simplicity for drug loading, organic nanoparticles (NPs), including liposomes, nanoemulsions, micelles, polymersomes, dendrimers, polymer conjugates and polymeric particles, have demonstrated tremendous potential for use in the efficient delivery of iodinated contrast media (ICMs). Herein, we comprehensively summarized the strategies and applications of organic NPs, especially polymer-based NPs, for the delivery of ICMs in CT imaging. We mainly focused on the use of polymeric nanoplatforms to prolong circulation time, reduce toxicity and enhance the targetability of ICMs. The emergence of some new technologies, such as theragnostic NPs and multimodal imaging and their clinical translations, are also discussed.


2020 ◽  
Vol 21 (1) ◽  
pp. 351-372 ◽  
Author(s):  
Taila Hartley ◽  
Gabrielle Lemire ◽  
Kristin D. Kernohan ◽  
Heather E. Howley ◽  
David R. Adams ◽  
...  

Accurate diagnosis is the cornerstone of medicine; it is essential for informed care and promoting patient and family well-being. However, families with a rare genetic disease (RGD) often spend more than five years on a diagnostic odyssey of specialist visits and invasive testing that is lengthy, costly, and often futile, as 50% of patients do not receive a molecular diagnosis. The current diagnostic paradigm is not well designed for RGDs, especially for patients who remain undiagnosed after the initial set of investigations, and thus requires an expansion of approaches in the clinic. Leveraging opportunities to participate in research programs that utilize new technologies to understand RGDs is an important path forward for patients seeking a diagnosis. Given recent advancements in such technologies and international initiatives, the prospect of identifying a molecular diagnosis for all patients with RGDs has never been so attainable, but achieving this goal will require global cooperation at an unprecedented scale.


The Lancet ◽  
1990 ◽  
Vol 335 (8686) ◽  
pp. 368-371 ◽  
Author(s):  
Taizo Nitta ◽  
Hideo Yagita ◽  
Ko Okumura ◽  
Kiyoshi Sato ◽  
Shozo Ishii

2020 ◽  
Vol 8 ◽  
Author(s):  
Carla S. D'Angelo ◽  
Azure Hermes ◽  
Christopher R. McMaster ◽  
Elissa Prichep ◽  
Étienne Richer ◽  
...  

Advances in omics and specifically genomic technologies are increasingly transforming rare disease diagnosis. However, the benefits of these advances are disproportionately experienced within and between populations, with Indigenous populations frequently experiencing diagnostic and therapeutic inequities. The International Rare Disease Research Consortium (IRDiRC) multi-stakeholder partnership has been advancing toward the vision of all people living with a rare disease receiving an accurate diagnosis, care, and available therapy within 1 year of coming to medical attention. In order to further progress toward this vision, IRDiRC has created a taskforce to explore the access barriers to diagnosis of rare genetic diseases faced by Indigenous peoples, with a view of developing recommendations to overcome them. Herein, we provide an overview of the state of play of current barriers and considerations identified by the taskforce, to further stimulate awareness of these issues and the passage toward solutions. We focus on analyzing barriers to accessing genetic services, participating in genomic research, and other aspects such as concerns about data sharing, the handling of biospecimens, and the importance of capacity building.


Sign in / Sign up

Export Citation Format

Share Document