Gene Therapy to Create Biological Pacemakers - Biopacemaking - page 90

8 Conclusions
For more than a decade, most of the cardiac gene therapy research has focused on Ad
vectors. If a bio-logical pacemaker is to challenge the current standard of an
electronic pacemaker, a long-term expression system is needed. For this purpose,
lentiviral vectors may be the most suitable, but further research is needed to evaluate
if stable, long-term, pacemaker function can be initiated by HCN-gene delivery from
these vectors. The electric coupling between gene therapy targeted and surrounding
cells, is another major research area that needs to be explored. Human mesenchymal
or embryonic stem cells could also provide a useful tool here to alter and control this
electrical coupling.
Bioengineered HCN channels have great potential. Although these channels are
still in an early stage of development, they may allow fine-tuning of the heart rate
range, making the clinical perspective of biological pacemakers increasingly realistic.
Acknowledgments. This work was supported by the Netherlands Heart Foundation
(NHS 2005B180 to HLT and JMTdB), the Royal Netherlands Academy of Arts and
Sciences KNAW (HLT), and the Bekales Foundation (HLT).
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