Albumin-binding RNAi Conjugate for Carrier Free Treatment of Arthritis.
Juan M ColazoElla N HoogenboezemVeeraj ShahFang YuJustin Han-Je LoAlexander G SoretsNora FranciniHongsik ChoDanielle L MichellKasey C VickersKatherine N Gibson-CorleyKaren A HastyLeslie CroffordRebecca S CookCraig L DuvallPublished in: bioRxiv : the preprint server for biology (2023)
Lipophilic siRNA conjugates optimized for albumin binding and "hitchhiking" can be leveraged to achieve preferential delivery to and gene silencing activity within arthritic joints. Chemical stabilization of the lipophilic siRNA enables intravenous siRNA delivery without lipid or polymer encapsulation. Using siRNA sequences targeting MMP13, a key driver of arthritis-related inflammation, albumin hitchhiking siRNA diminished MMP13, inflammation, and manifestations of osteoarthritis and rheumatoid arthritis at molecular, histological, and clinical levels, consistently outperforming clinical standards of care and small molecule MMP antagonists.
Keyphrases
- cancer therapy
- rheumatoid arthritis
- small molecule
- drug delivery
- oxidative stress
- healthcare
- hyaluronic acid
- disease activity
- cell migration
- dna binding
- palliative care
- ankylosing spondylitis
- interstitial lung disease
- low dose
- idiopathic pulmonary fibrosis
- transcription factor
- binding protein
- knee osteoarthritis
- fatty acid
- replacement therapy