Explore the vast range of titles available.

RNA therapy for eye diseases has good clinical translation potential, benefiting from the eye’s immune privilege, local drug delivery, and minimal dosage needs.RNA therapeutics play a crucial role in the treatment of genetic ocular diseases, which are directly linked to gene regulation.Delivering RNA to the eye’s posterior segment necessitates combination of delivery carriers and technology for effective in situ therapy.RNA nanomedicines have been utilized to reach specific targets in clinical treatments for eye diseases.Sequencing technology can deepen our understanding of eye diseases, revealing new diagnostic markers and therapeutic targets. Ocular disorders remain a major global health challenge with unmet medical needs. RNA nanomedicine has shown significant therapeutic benefits and safety profiles in patients with complex eye disorders, already benefiting numerous patients with gene-related eye disorders. The effective delivery of RNA to the unique structure of the eye is challenging owing to RNA instability, off-target effects, and ocular physiological barriers. Specifically tailored RNA medication, coupled with sophisticated engineered delivery platforms, is crucial to guide and advance developments in treatments for oculopathy. Herein we review recent advances in RNA-based nanomedicine, innovative delivery strategies, and current clinical progress and present challenges in ocular disease therapy. Ocular disorders remain a major global health challenge with unmet medical needs. RNA nanomedicine has shown significant therapeutic benefits and safety profiles in patients with complex eye disorders, already benefiting numerous patients with gene-related eye disorders. The effective delivery of RNA to the unique structure of the eye is challenging owing to RNA instability, off-target effects, and ocular physiological barriers. Specifically tailored RNA medication, coupled with sophisticated engineered delivery platforms, is crucial to guide and advance developments in treatments for oculopathy. Herein we review recent advances in RNA-based nanomedicine, innovative delivery strategies, and current clinical progress and present challenges in ocular disease therapy.

RNA-based nanomedicines encompass a range of therapeutic approaches that utilize RNA molecules or molecules that target RNAs for the treatment or prevention of diseases. These include antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), endogenous microRNAs (miRNAs), messenger RNAs (mRNAs), clustered regularly interspersed short palindromic repeats-associated protein 9 (CRISPR/Cas9), single guide RNAs (sgRNAs), as well as RNA aptamers. These therapeutic agents exert their effects through various mechanisms such as gene inhibition, addition, replacement, and editing. The advancement of RNA biology and the field of RNA therapy has paved the way for the development and utilization of RNA-based nanomedicine in human healthcare. One remarkable example of RNA-based nanomedicine is the mRNA-based vaccines including mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech) that have been successfully employed in response to the coronavirus disease 2019 (COVID-19) pandemic. This review aims to highlight the advantages of RNA-based nanomedicines, provides an overview of significant developments in delivery systems, elucidates the molecular mechanisms of action underlying RNA-based nanomedicines, and discusses their clinical applications. Additionally, the review will address the existing challenges and innovations in delivery platforms while exploring the future possibilities for these promising RNA-based nanomedicines.

Exosomes (versatile, cell-derived nanovesicles naturally endowed with exquisite target-homing specificity and the ability to surmount in vivo biological barriers) hold substantial promise for developing exciting approaches in drug delivery and cancer immunotherapy. Specifically, bioengineered exosomes are being successfully deployed to deliver potent tumoricidal drugs (siRNAs and chemotherapeutic compounds) preferentially to cancer cells, while a new generation of exosome-based therapeutic cancer vaccines has produced enticing results in early-phase clinical trials. Here, we review the state-of-the-art technologies and protocols, and discuss the prospects and challenges for the clinical development of this emerging class of therapeutics. Exosomes are extracellular cell-derived phospholipid nanovesicles that function as signalosomes, transmitting prodigious amounts of bioactive molecules to specific recipient tissues. Their intriguing endogenous functionalities have galvanized momentous efforts to exploit them as novel anticancer therapeutics. Exosomes may offer a tractable, bioinspired system for targeted drug delivery, which could improve the therapeutic indices of conventional cytotoxic chemotherapeutic agents, and help to realize the enormous potential of gene therapy in oncology. Owing to their immunomodulatory potential, exosomes may also be deployed in innovative immunological approaches to activate adaptive and innate effector cell-mediated anticancer immunosurveillance.

Carriers of genetic material are divided into vectors of viral and non-viral origin. Viral carriers are already successfully used in experimental gene therapies, but despite advantages such as their high transfection efficiency and the wide knowledge of their practical potential, the remaining disadvantages, namely, their low capacity and complex manufacturing process, based on biological systems, are major limitations prior to their broad implementation in the clinical setting. The application of non-viral carriers in gene therapy is one of the available approaches. Poly(amidoamine) (PAMAM) dendrimers are repetitively branched, three-dimensional molecules, made of amide and amine subunits, possessing unique physiochemical properties. Surface and internal modifications improve their physicochemical properties, enabling the increase in cellular specificity and transfection efficiency and a reduction in cytotoxicity toward healthy cells. During the last 10 years of research on PAMAM dendrimers, three modification strategies have commonly been used: (1) surface modification with functional groups; (2) hybrid vector formation; (3) creation of supramolecular self-assemblies. This review describes and summarizes recent studies exploring the development of PAMAM dendrimers in anticancer gene therapies, evaluating the advantages and disadvantages of the modification approaches and the nanomedicine regulatory issues preventing their translation into the clinical setting, and highlighting important areas for further development and possible steps that seem promising in terms of development of PAMAM as a carrier of genetic material.

The regulatory approval of Onpattro, a lipid nanoparticle-based short interfering RNA drug for the treatment of polyneuropathies induced by hereditary transthyretin amyloidosis, paves the way for clinical development of many nucleic acid-based therapies enabled by nanoparticle delivery.

Cancer treatment has been revolutionized by immunotherapy and nanomedicine, offering innovative strategies to overcome the tumor microenvironment (TME) complexities. However, challenges such as therapeutic resistance, off-target effects, and immune suppression necessitate advanced delivery systems and combination approaches. Recent advancements in nanoparticle-based therapies, biomimetic platforms, and personalized immunotherapy provide promising solutions to enhance therapeutic efficacy while minimizing systemic toxicity. This review explores recent nanoparticle-mediated immunotherapy developments, highlighting strategies to optimize drug delivery, remodel the TME, and improve patient-specific treatment outcomes. A comprehensive review of recent literature focused on nanoparticle-based drug delivery, stimuli-responsive systems, biomimetic nanoplatforms, and personalized immunotherapy approaches. The effectiveness of combination therapies integrating physical and immunological strategies was also analyzed. Nanoparticle-mediated immunotherapy enables precise targeting and controlled drug release, significantly improving therapeutic outcomes. Biomimetic nanoplatforms enhance immune modulation and drug bioavailability, while personalized immunotherapy, guided by predictive biomarkers, tailors treatment to individual patients. Advanced nanomedicine strategies, including TME remodeling, targeted genome editing, and combination immunotherapies, offer promising avenues for overcoming limitations in conventional cancer treatments. Future research should optimize nanoformulations, integrate multi-modal treatment strategies, and refine biomarker-driven personalization to enhance clinical outcomes.

Extracellular vesicles (EVs) include a variety of nanosized vesicles released to the extracellular microenvironment by the vast majority of cells transferring bioactive lipids, proteins, mRNA, miRNA or non-coding RNA, as means of intercellular communication. Remarkably, among other fields of research, their use has become promising for immunomodulation, tissue repair and as source for novel disease-specific molecular signatures or biomarkers. However, a major challenge is to define accurate, reliable and easily implemented techniques for EV isolation due to their nanoscale size and high heterogeneity. In this context, differential ultracentrifugation (dUC) has been the most widely used laboratory methodology, but alternative procedures have emerged to allow purer EV preparations with easy implementation. Here, we present and discuss the most used of the different EV isolation methods, focusing on the increasing impact of size exclusion chromatography (SEC) on the resulting EV preparations from in vitro cultured cells-conditioned medium and biological fluids. Comparatively, low protein content and cryo-electron microscopy analysis show that SEC removes most of the overabundant soluble plasma proteins, which are not discarded using dUC or precipitating agents, while being more user friendly and less time-consuming than gradient-based EV isolation. Also, SEC highly maintains the major EVs’ characteristics, including vesicular structure and content, which guarantee forthcoming applications. In sum, together with scaling-up possibilities to increase EV recovery and manufacturing following high-quality standards, SEC could be easily adapted to most laboratories to assist EV-associated biomarker discovery and to deliver innovative cell-free immunomodulatory and pro-regenerative therapies.

The COVID-19 pandemic has left scientists and clinicians no choice but a race to find solutions to save lives while controlling the rapid spreading. Messenger RNA (mRNA)-based vaccines have become the front-runners because of their safety profiles, precise and reproducible immune response with more cost-effective and faster production than other types of vaccines. However, the physicochemical properties of naked mRNA necessitate innovative delivery technologies to ferry these ‘messengers’ to ribosomes inside cells by crossing various barriers and subsequently induce an immune response. Intracellular delivery followed by endosomal escape represents the key strategies for cytoplasmic delivery of mRNA vaccines to the target. This Perspective provides insights into how state-of-the-art nanotechnology helps break the delivery barriers and advance the development of mRNA vaccines. The challenges remaining and future perspectives are outlined.

Messenger RNA (mRNA) is an emerging class of therapeutic agent for the prevention and treatment of a wide range of diseases. The recent success of the two highly efficacious mRNA vaccines produced by Moderna and Pfizer–BioNTech to protect against COVID-19 highlights the huge potential of mRNA technology for revolutionizing life science and medical research. Challenges related to mRNA stability and immunogenicity, as well as in vivo delivery and the ability to cross multiple biological barriers, have been largely addressed by recent progress in mRNA engineering and delivery. In this Review, we present the latest advances and innovations in the growing field of mRNA nanomedicine, in the context of ongoing clinical translation and future directions to improve clinical efficacy. The COVID-19 mRNA vaccines have transformed the field of mRNA nanomedicine, but this new class of therapeutics has the potential to treat many other diseases. This Review profiles the latest advances and challenges.

Despite progress in systemic small interfering RNA (siRNA) delivery to the liver and to solid tumors, systemic siRNA delivery to leukocytes remains challenging. The ability to silence gene expression in leukocytes has great potential for identifying drug targets and for RNAi-based therapy for leukocyte diseases. However, both normal and malignant leukocytes are among the most difficult targets for siRNA delivery as they are resistant to conventional transfection reagents and are dispersed in the body. We used mantle cell lymphoma (MCL) as a prototypic blood cancer for validating a novel siRNA delivery strategy. MCL is an aggressive B-cell lymphoma that overexpresses cyclin D1 with relatively poor prognosis. Down-regulation of cyclin D1 using RNA interference (RNAi) is a potential therapeutic approach to this malignancy. Here, we designed lipid-based nanoparticles (LNPs) coated with anti-CD38 monoclonal antibodies that are specifically taken up by human MCL cells in the bone marrow of xenografted mice. When loaded with siRNAs against cyclin D1, CD38-targeted LNPs induced gene silencing in MCL cells and prolonged survival of tumor-bearing mice with no observed adverse effects. These results highlight the therapeutic potential of cyclin D1 therapy in MCL and present a novel RNAi delivery system that opens new therapeutic opportunities for treating MCL and other B-cell malignancies.