Biomedical Engineering Reference
In-Depth Information
demonstrates that siRNA-mediated mRNA cleavage occurs specifically at the
predicted site was detectable in a high-dose treated patient [
235
]. Together, these
data demonstrate that systemically administered siRNA can produce a specific gene
inhibition (reduction in mRNA and protein) by an RNA interference mechanism in
humans. These data present an important and encouraging step in the slow process
of transferring ideas into medicines. It has to be mentioned that it took 20 years
from the design of Tf-targeting polyplexes [
97
] to the demonstration of direct
molecular effects in humans [
235
].
5 Conclusions
Over more than two decades of development, functional polymer conjugates have
become useful carriers for drug and nucleic acid delivery. Dynamic, bioresponsive
polymers have been designed that can better cope with the multiple sequential
delivery steps. Improved chemistry is able to provide monodisperse polymer
structures with defined size, topology, and transport domains [
236
,
237
]. This
will also be essential for practical development reasons, including production of
clinical grade materials according to good manufacturing practice guidelines. The
first polymeric carriers have already entered clinical testing, with encouraging
results. It will be very interesting to see how successfully they will fill clinical
development pipelines in the upcoming future.
Acknowledgments Many thanks to Olga Br
uck (LMU) for skillful assistance in preparing the
review. Our own work in the reviewed research area was supported by the German DFG
excellence cluster “Nanosystems Initiative Munich (NIM)” and the BMBF Munich Biotech cluster
m4 project T12.
€
References
1. Duncan R (2003) The dawning era of polymer therapeutics. Nat Rev Drug Discov 2:347-360
2. Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL (1990) Direct
gene transfer into mouse muscle in vivo 726. Science 247:1465-1468
3. Caplen NJ, Alton EW, Middleton PG, Dorin JR, Stevenson BJ, Gao X, Durham SR, Jeffery
PK, Hodson ME, Coutelle C (1995) Liposome-mediated CFTR gene transfer to the nasal
epithelium of patients with cystic fibrosis. Nat Med 1:39-46
4. Heller LC, Heller R (2006) In vivo electroporation for gene therapy. Hum Gene Ther
17:890-897
5. Tjelle TE, Rabussay D, Ottensmeier C, Mathiesen I, Kjeken R (2008) Taking electroporation-
based delivery of DNA vaccination into humans: a generic clinical protocol. Methods Mol
Biol 423:497-507
6. Sidi AA, Ohana P, Benjamin S, Shalev M, Ransom JH, Lamm D, Hochberg A, Leibovitch I
(2008) Phase I/II marker lesion study of intravesical BC-819 DNA plasmid in H19 over
expressing superficial bladder cancer
refractory to bacillus Calmette-Guerin. J Urol
180:2379-2383
