<s>
Tbx18	B-Algorithm
transduction	I-Algorithm
is	O
a	O
method	O
of	O
turning	O
on	O
genes	O
in	O
heart	O
muscle	O
cells	O
as	O
a	O
treatment	O
for	O
certain	O
cardiac	B-Application
arrhythmias	I-Application
.	O
</s>
<s>
Tbx18	O
gene	O
therapy	O
is	O
aimed	O
at	O
treating	O
a	O
group	O
of	O
arrhythmias	B-Application
known	O
as	O
sick	B-Algorithm
sinus	I-Algorithm
syndrome	I-Algorithm
.	O
</s>
<s>
In	O
a	O
healthy	O
heart	O
,	O
sinoatrial	O
(	O
SA	O
)	O
nodal	O
cells	O
act	O
as	O
the	O
heart	O
’s	O
pacemaker	B-Device
and	O
cause	O
the	O
heart	O
to	O
beat	O
in	O
a	O
regular	O
rhythm	O
.	O
</s>
<s>
The	O
problem	O
in	O
sick	B-Algorithm
sinus	I-Algorithm
syndrome	I-Algorithm
is	O
that	O
the	O
SA	O
node	O
is	O
not	O
functioning	O
properly	O
and	O
is	O
causing	O
an	O
irregular	B-Application
heartbeat	I-Application
.	O
</s>
<s>
Currently	O
the	O
treatment	O
for	O
sick	B-Algorithm
sinus	I-Algorithm
syndrome	I-Algorithm
is	O
to	O
remove	O
the	O
SA	O
nodal	O
cells	O
that	O
are	O
not	O
functioning	O
properly	O
(	O
?	O
)	O
</s>
<s>
and	O
to	O
implant	O
an	O
electronic	B-Device
pacemaker	I-Device
to	O
maintain	O
a	O
regular	O
rhythm	O
.	O
</s>
<s>
The	O
Tbx18	O
gene	O
is	O
required	O
for	O
development	O
of	O
pacemaker	B-Device
cells	O
in	O
the	O
heart	O
during	O
fetal	O
development	O
but	O
is	O
normally	O
not	O
functional	O
after	O
birth	O
.	O
</s>
<s>
Tbx18	B-Algorithm
transduction	I-Algorithm
converts	O
atrial	O
muscle	O
cells	O
into	O
SA	O
node	O
cells	O
that	O
initiate	O
the	O
heartbeat	O
.	O
</s>
<s>
Adenoviral	O
TBX18	O
gene	O
transfer	O
could	O
create	O
biological	O
pacemaker	B-Device
activity	O
in	O
vivo	O
in	O
a	O
large-animal	O
model	O
of	O
complete	O
heart	O
block	O
.	O
</s>
<s>
Biological	O
pacemaker	B-Device
activity	O
,	O
originating	O
from	O
the	O
intramyocardial	O
injection	O
site	O
,	O
was	O
evident	O
in	O
TBX18-transduced	O
animals	O
starting	O
at	O
day	O
2	O
and	O
persisted	O
for	O
the	O
duration	O
of	O
the	O
study	O
(	O
14	O
days	O
)	O
with	O
minimal	O
backup	O
electronic	B-Device
pacemaker	I-Device
use	O
.	O
</s>
<s>
Thus	O
,	O
minimally	O
invasive	O
TBX18	O
gene	O
transfer	O
creates	O
physiologically	O
relevant	O
pacemaker	B-Device
activity	O
in	O
complete	O
heart	O
block	O
,	O
providing	O
evidence	O
for	O
therapeutic	O
somatic	O
reprogramming	O
in	O
a	O
clinically	O
relevant	O
disease	O
model	O
.	O
</s>
<s>
The	O
currently	O
used	O
electronic	B-Device
pacemakers	I-Device
have	O
drawbacks	O
such	O
as	O
equipment	O
malfunction	O
,	O
limited	O
battery	O
life	O
,	O
lack	O
of	O
nervous	O
system	O
regulation	O
,	O
and	O
risks	O
associated	O
with	O
implantation	O
of	O
the	O
device	O
in	O
one	O
’s	O
chest	O
.	O
</s>
<s>
Creation	O
of	O
a	O
biological	O
pacemaker	B-Device
could	O
prove	O
to	O
be	O
a	O
feasible	O
alternative	O
that	O
eliminates	O
some	O
of	O
the	O
problems	O
associated	O
with	O
electronic	B-Device
pacemakers	I-Device
.	O
</s>
<s>
Various	O
gene	O
and	O
cell-based	O
approaches	O
of	O
creating	O
a	O
biological	O
pacemaker	B-Device
have	O
been	O
looked	O
at	O
over	O
the	O
last	O
few	O
years	O
.	O
</s>
