Ultrasound targeting of Q-starch/miR-197 complexes for topical treatment of psoriasis

Psoriasis is one of the most common chronic inflammatory skin disorders, with cutaneous and systemic manifestations and substantial negative effects on affected patients' quality of life. [1] MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression. [2] Recent studies have revealed that interactions between miRNAs and their targets play critical roles in regulating distinct signalling pathways during skin differentiation. [3,4] Evidence is rapidly accumulating for the roles of miRNAs in the pathogenesis of inflammatory skin disorders. [5][6][7] In previous studies, others and we have shown that miR-197-3p (hereafter named miR-197) expression is downregulated in the psoriatic lesions compared to normal or uninvolved psoriatic skin. [6,8] Moreover, we showed that miR-197 modulates IL-22 and IL-17 signalling in normal keratinocytes (KC). Specifically, we found that both IL-22 and IL-17 activated the transcription of miR-197, and miR-197 targets and inhibits the expression of both the IL22RA1 subunit of

show abstract

“…Indeed, we have shown that miR-197 has potential as therapeutic agent in psoriasis. [12] ACK N OWLED G EM ENTS…”

Section: Discussionmentioning

confidence: 99%

“…[9] Therefore, miR-197 was suggested and demonstrated as a potential therapeutic agent for psoriasis. [12] miR-197 is located at the p13.3 region of chromosome 1, within an exon transcribing the 3'UTR of the gene GNAI3. Although it is part of a protein-coding gene, it likely has its own promoter.…”

mentioning

confidence: 99%

IL6R is a target of miR‐197 in human keratinocytes

Masalha

Gur‐Wahnon

Meningher

et al. 2020

Experimental Dermatology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Low frequency ultrasound has been implemented to enhance dermal penetration of quaternized starch and miR-197 (a microRNA targeting subunits of IL-17 and IL-22 receptors) complexes. This showed a significant reduction in psoriatic levels when tested in a human skin xenograft model in mice 107 . Sonophoresis also enhanced the permeation of PAMAM and low molecular weight peptide dendrimers, while increased the dermal retention of high molecular weight peptide dendrimers 220 .…”

Section: State Of Clinical Translationmentioning

confidence: 92%

Formulation‐based approaches for dermal delivery of vaccines and therapeutic nucleic acids: Recent advances and future perspectives

Sallam

Prakash

Kumbhojkar

et al. 2021

Bioengineering & Transla Med

View full text Add to dashboard Cite

A growing variety of biological macromolecules are in development for use as active ingredients in topical therapies and vaccines. Dermal delivery of biomacromolecules offers several advantages compared to other delivery methods, including improved targetability, reduced systemic toxicity and decreased degradation of drugs. However, this route of delivery is hampered by the barrier function of the skin. Recently, a large body of research has been directed towards improving the delivery of macromolecules to the skin, ranging from nucleic acids to antigens, using noninvasive means. In this review, we discuss the latest formulation-based efforts to deliver antigens and nucleic acids for vaccination and treatment of skin diseases. We provide a perspective of their advantages, limitations and potential for clinical translation. The delivery platforms discussed in this review may provide formulation scientists and clinicians with a better vision of the alternatives for dermal delivery of biomacromolecules, which may facilitate the development of new patientfriendly prophylactic and therapeutic medicines.

show abstract

“…Sonoporation temporarily permeabilizes the cell membrane and facilitates the penetration of genetic cargo into cells [ 58 ]. As such, sonoporation enabled the topical penetration of miR -197 in psoriatic mouse models, followed by a significant downregulation of interleukin-17 (IL-17) and IL-22 receptors [ 59 ]. For intradermal delivery, low and medium ultrasound frequencies are used, yielding high ‘cavitational effects’ and triggering the formation of vapor-filled bubbles, which ultimately collapse and form pores in the cell membrane.…”

Section: Delivery Of Gene Therapies To the Skinmentioning

confidence: 99%

Gene Delivery to the Skin – How Far Have We Come?

Ain

Campos

Huynh

et al. 2021

Trends in Biotechnology

View full text Add to dashboard Cite

Gene therapies are powerful tools to prevent, treat, and cure human diseases. The application of gene therapies for skin diseases received little attention so far, despite the easy accessibility of skin and the urgent medical need. A major obstacle is the unique barrier properties of human skin, which significantly limits the absorption of biomacromolecules, and thus hampers the efficient delivery of nucleic acid payloads. In this review, we discuss current approaches, successes, and failures of cutaneous gene therapy and provide guidance toward the development of next-generation concepts. We specifically allude to the delivery strategies as the major obstacle that prevents the full potential of gene therapies – not only for skin disorders but also for almost any other human disease.

show abstract

Ultrasound targeting of Q-starch/miR-197 complexes for topical treatment of psoriasis

Cited by 28 publications

References 41 publications

IL6R is a target of miR‐197 in human keratinocytes

IL6R is a target of miR‐197 in human keratinocytes

Formulation‐based approaches for dermal delivery of vaccines and therapeutic nucleic acids: Recent advances and future perspectives

Gene Delivery to the Skin – How Far Have We Come?

Contact Info

Product

Resources

About