{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:02:04Z","timestamp":1787029324153,"version":"build-2736575974"},"reference-count":169,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Gene therapies have conspicuously bloomed in recent years as evidenced by the increasing number of cell-, gene-, and oligo-based approved therapies. These therapies hold great promise for dermatological disorders with high unmet need, for example, epidermolysis bullosa or pachyonychia congenita. Furthermore, the recent clinical success of clustered regularly interspaced short palindromic repeats (CRISPR) for genome editing in humans will undoubtedly contribute to defining a new wave of therapies. Like biologics, naked nucleic acids are denatured inside the gastrointestinal tract and need to be administered via injections. For a treatment to be effective, a sufficient amount of a given regimen needs to reach systemic circulation. Multiple companies are racing to develop novel oral drug delivery approaches to circumvent the proteolytic and acidic milieu of the gastrointestinal tract. In this review, we provide an overview of the evolution of the gene therapy landscape, with a deep focus on gene and oligonucleotide therapies in clinical trials aimed at treating skin diseases. We then examine the progress made in drug delivery, with particular attention on the peptide field and drug-device combinations that deliver macromolecules into the gastrointestinal tract. Such novel devices could potentially be applied to administer other therapeutics including genes and CRISPR-based systems.<\/jats:p>","DOI":"10.3390\/pharmaceutics13101722","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T21:31:26Z","timestamp":1634765486000},"page":"1722","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Future Perspectives of Oral Delivery of Next Generation Therapies for Treatment of Skin Diseases"],"prefix":"10.3390","volume":"13","author":[{"given":"Pia Pernille","family":"S\u00f8gaard","sequence":"first","affiliation":[{"name":"Regenerative Medicine Department, LEO Pharma A\/S, Industriparken 55, 2750 Ballerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0188-5408","authenticated-orcid":false,"given":"Marianne","family":"Lind","sequence":"additional","affiliation":[{"name":"Explorative Formulation and Technologies, LEO Pharma A\/S, Industriparken 55, 2750 Ballerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chatpakorn Rassemeena","family":"Christiansen","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Department, LEO Pharma A\/S, Industriparken 55, 2750 Ballerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Petersson","sequence":"additional","affiliation":[{"name":"Explorative Formulation and Technologies, LEO Pharma A\/S, Industriparken 55, 2750 Ballerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6381-324X","authenticated-orcid":false,"given":"Adam","family":"Clauss","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Department, LEO Pharma A\/S, Industriparken 55, 2750 Ballerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2844-7598","authenticated-orcid":false,"given":"Ester","family":"Caffarel-Salvador","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Department, LEO Pharma A\/S, Industriparken 55, 2750 Ballerup, Denmark"},{"name":"LEO Science & Tech Hub, One Broadway, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/cgt.2016.4","article-title":"Precise and efficient siRNA design: A key point in competent gene silencing","volume":"23","author":"Fakhr","year":"2016","journal-title":"Cancer Gene Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/s41573-020-0075-7","article-title":"Advances in oligonucleotide drug delivery","volume":"19","author":"Roberts","year":"2020","journal-title":"Nat. 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