Until the year 2000 the research focus of the Laboratory of General Biochemistry and Physical Pharmacy was almost completely on physicochemical aspects of pharmaceutical enzymes , being the first biological drugs and a long standing research theme of our previous lab directors. Being convinced that nucleic acids (NAs) would become the ‘future biological medication’ and being fascinated by the power of nanotechnology, Prof. Stefaan De Smedt installed the Ghent Research Group on Nanomedicines and initiated nano-technological research for the delivery of nucleic acids  in the Laboratory of General Biochemistry and Physical Pharmacy almost 20 years ago. 

Nucleic acid bio-therapeutics. Progress in the fundamental understanding of RNA biology has led to the identification of new RNA classes with unanticipated functions.Following these advances in molecular biology, new therapeutic strategies based on nucleic acids have been introduced. Examples of such NAs are single stranded antisense oligonucleotides (ASOs), double stranded small interfering RNAs (siRNAs) and microRNAs (miRNAs), all for inhibiting gene expression and, most recently, single guide RNAs (sgRNAs) for the editing of mutated genes. In addition to NAs which silence or edit genes, there is also a major interest in the therapeutic potential of messenger RNAs (mRNAs) to express proteins in cells for e.g. vaccination purposes.

As 30-40 years ago, when recombinant proteins and mABs began to be developed as therapeutic molecules, it seems that with nucleic acid bio-therapeutics we are again on the brink of a revolution in drug development. This seems from the many ongoing trials in which various types of NAs are clinically evaluated. This is also apparent from the recent landmark approvals of the first (i) ASOs like Spinraza (intrathecally injected against spinal muscular atrophy) and Exondys 51 (against Duchenne’s muscular dystrophy) and (ii) siRNA drug Onpattro (intravenously injected siRNA to silence the synthesis of the transthyretin protein in the liver to treat amyloidosis). It is very well justified to say that in the near to midterm future nucleic acid bio-therapeutics will increasingly appear in pharmacopoeia, expanding the universe of therapeutic targets

Nanomedicines. Nanomedicines can be defined as well designed nanoscopic particles (size of viruses) loaded with drugs. Challenges are to design nanomedicines in such a way that, after mucosal or parenteral administration, they deliver their drug load in a most efficient way in diseased cells. Even though the medical potential of nanomedicines is regarded as tremendous by many, a large gap remains between the scientific advances in the field and their translation into patient benefits.

Currently the Laboratory of General Biochemistry & Physical Pharmacy houses 4 closely collaborating research groups: the Biophotonic Research Group, the Ocular Delivery Group, the Lung Delivery Group and the Vaccine Delivery Group. The global research focus of our teams is on the delivery of bio-therapeutics, especially nucleic acids. Our teams offer a multifaceted portfolio of competencies including  pharmacology, material knowledge and expertise in drug delivery, nanotechnology, cell biology, immunology, biophysics, optics and bio-photonics. Together with partners in academia and industry we develop and evaluate delivery concepts and technologies for novel advanced therapies. A variety of large-scale projects funded by the European Community, the Flemish Fund for Scientific Research (FWO),  Flanders Innovation & Entrepreneurship (VLAIO), the Special Research Fund of UGent (BOF) and the Industrial Fund of UGent (IOF) have created a high level of cooperation with colleagues from UGent, other Belgian universities and institutes from all over Europe.

_{Delivery strategies and targets investigated in the lab. (A) Cell membranes are largely impermeable for NAs. (B) Various strategies are investigated to facilitate intracellular delivery of NAs. One of those is the encapsulation of NAs in nanoscopic particles (‘nanomedicines’; tens to hundreds of nanometers in size) which can guide NAs into cells through endocytosis. However, efficient escape of nanomedicines from endo-lysosomal vesicles into the cytosol remains a major hurdle. (C) Another strategy is the use of physical forces like light, electric fields (electroporation), mechanical forces… to ‘mildly’ disrupt cell membranes to allow ‘direct’ delivery of NAs into the cytosol, thus by-passing endo-lysosomal vesicles. We focus on nanomedicines for NA delivery into eyes, lungs and dendritic cells (for vaccination) and on light-mediated delivery of NAs in immune cells for the purpose of cell therapy}