Lentiviral construction to deliver tgf-β3 and knock down type I collagen expression for cartilage therapy.

Abstract

Articular cartilage is avascular, and thus, when damaged, will not be able to heal itself. First-line treatment commonly used for articular cartilage disorder aimed to relieve pain from patient while the full recovery is yet to be achieved. Cell therapy is known to have potentials in replicating the function and structure of cartilage tissues. It has been proven that the differentiation of synovial mesenchymal stem cells (SMSC) into chondrocytes can be promoted by supplementing transforming growth factor β3 (TGF-β3). Unfortunately, the drawback of using synovial mesenchymal stem cells for treatment is the undesired expression of collagen type I. Presence of collagen type I will hinder the biomechanical strength of the cartilage. To be able to provide sustained TGF-β3 and suppress collagen type I in vivo, we are going to implement gene therapy approach. One strategy is to transduce the SMSC with lentiviruses that have been genetically modified. Gene of interest for TGF-β3 expression is inserted into the lentiviral vector. RNA interference (RNAi) strategy is applied to produce small-hairpin RNA (shRNA) that will block the expression of collagen type I. The DNA fragment responsible for shRNA production is integrated into the lentiviral vector as well. Together with biomaterials, we will engineer a 3-dimensional construct of SMSC that is able to deliver TGF-β3 and knock down type I collagen expression for the purpose of cartilage therapy.