WILT: still crazy after both these years?
A.D.N.J. de Grey
Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK
Two years ago, at the first SENS conference (IABG 10), I presented a
decidedly ambitious proposal for combating cancer much more thoroughly
than can realistically be expected from any therapy currently existing
or under development. This concept, termed "Whole-body Interdiction
of Lengthening of Telomeres" (WILT), has two main components: (a) the
deletion from as many as possible of our cells of the genes involved
in telomere elongation by either of the pathways seen in human cancers
and (b) the pre-emption of deleterious side-effects in continuously
renewing tissues by the decadal reseeding of those tissues' stem cell
pools with engineered stem cells that also lack those genes but have
had their telomeres extended ex vivo with exogenous telomerase. This
is clearly the most ambitious compoinent of my SENS (Strategies for
Engineered Negligible Senescence) scheme for the piecemeal repair of
age-related molecular and cellular damage. Yet, despite increasingly
intensive scrutiny, there remains no clear reason why it should fail.
I will summarise the WILT concept and then discuss some of the more
complex issues surrounding its feasibility.
Key words:
WILT, cancer, telomeres, telomerase, ALT, gene targeting, stem cell therapy
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