Historically, my research interests have concerned lipoprotein metabolism and cell membrane lipids, which over the years have had broad relevance to liver disease and also to cardiovascular, renal, parasitological, viral and neurological diseases. In the last 10-15 years, the focus has been on gene therapy strategies to counteract deficient or dysfunctional HDL-proteins (ApoAI, ApoE or LCAT). This included gene addition using nonviral (plasmids) and viral (recombinant adenovirus and adeno-associated virus [AAV]) vectors, with a recent emphasis on self-complementary AAV8.

In parallel, we have advanced the emerging technology of in-situ gene editing using synthetic oligonucleotides. Potential applications include introducing disease-associated mutations into cell lines or animals, functional studies of SNPs and, ultimately, clinical therapy by correcting genetic point mutations. A key target is correction of the dysfunctional e2 and e4 alleles (UK frequency 0.08 & 0.15), which are risk factors for arteriosclerosis and Alzheimer's disease. This application of oligonucleotide therapeutics is being extended to encompass exon splicing and spliceosome-mediated RNA transplicing (SMaRT) technologies to treat genetic elevation of plasma LDL.