Syahril Abdullah

Research Overview

The main focus of our research team is on the development of gene and stem cell therapy with the primary aim of developing treatment for a blood disorder. Over the past few years, we have been focusing our efforts to overcome problems such as; (1) extending the duration of therapeutic gene expression and, (2) improving the safety features of the gene delivery vectors. 

We have found that the transgene expression in hematopoietic stem cells mediated by Lentiviral gene delivery was transient in vitro and following transplantation into mice. This was due to the epigenetic influences at the regulatory sequence and the reporter gene, together with the effects at the chromatin level.  To overcome this problem, we have tested a Lentiviral vector carrying zero-CpG reporter gene. Unfortunately, the results were modest. Further refinement on the Lentiviral construct is being done. We are also in the midst of transducing pluripotent cell lines to determine the transgene expression profiles and to study the epigenetic influences on the transgene. 

Our group has recently generated induced Pluripotent Stem cell (iPS cells) line from mouse-tail fibroblast using a polycistron Lentiviral vector carrying four transcription factors. With the ability to produce such cell, we envision to combine the gene therapy approach with iPS cells for safe, effective and permanent disease correction.        

Improvement in the duration of transgene expression and safety features have been shown with the use of CpG depleted non-viral vector in many organs. Such vector is currently used in a clinical trial for Cystic Fibrosis gene therapy in the United Kingdom. Our group is studying the CpG-depleted non-viral vector to determine its effectiveness in different models and to ascertain the mechanisms of prolonged transgene expression.      

The ability of adult cells to trans-differentiate into a different type of cells by natural mean in culture is also intriguing. We are learning this process in hope to be able to produce and isolate our cell of interest in the near future.

We are also interested in discovering novel gene carrier to the lung. At the moment, we are focusing our research on nanoparticles such as dextran-spermine and carbonate apatite. We hope that plasmid DNA encapsulated into a nanosized particle will enter the lung cells more efficiently compared to its larger-sized counterparts.

Research Funding

Selected Publications

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Awards

Patents

Current Lab Members