STRATEGIES FOR DELIVERY

Part I: Endcaps are linkers that link the 3 and 5
ends of DNA duplexes. A series of diamide endcaps
has been synthesized and shown to stabilize DNA
duplexes (4 base-pair). Endcapped CpG
oligonucleotides were synthesized to elucidate the
mode of recognition of different forms of CpG
oligonucleotides by the immune system. Endcapped CpG
oligonucleotides stimulated IL-6 and IL-12 secretion
and extended the life span of the tumor implanted
mice beyond that of the untreated control mice.
Closed endcapped DNA duplexes were obtained by
enzymatic ligation of the nicked DNA duplexes. The
efficiency of ligation was dependent on the number
of nucleotides flanking the 3 - and 5 ends of the
nick. The nuclease stability of endcapped CpG
oligonucleotides was established to be at least 6-
fold more stable than unmodified oligonucleotides.
Part II: Thiol terminated amine and guanidinium
derivatives were synthesized and conjugated to 5 nm
and 10 nm gold nanoparticles. These functionalized
gold colloids were studied for their cellular uptake.

Autorentext

Pei-Sze Ng joined a biotechnology company in Cambridge, MA, as a scientist after completion of her post-doctorate training at the Massachusetts Institute of Technology. From 1999 to 2004, she did her doctoral work in the field of medicinal chemistry and biotechnology at Purdue University, Indiana, U.S.A. Her family lives in Singapore.

Klappentext

Part I: Endcaps are linkers that link the 3' and 5' ends of DNA duplexes. A series of diamide endcaps has been synthesized and shown to stabilize DNA duplexes (4 base-pair). Endcapped CpG oligonucleotides were synthesized to elucidate the mode of recognition of different forms of CpG oligonucleotides by the immune system. Endcapped CpG oligonucleotides stimulated IL-6 and IL-12 secretion and extended the life span of the tumor implanted mice beyond that of the untreated control mice. Closed endcapped DNA duplexes were obtained by enzymatic ligation of the nicked DNA duplexes. The efficiency of ligation was dependent on the number of nucleotides flanking the 3'- and 5' ends of the nick. The nuclease stability of endcapped CpG oligonucleotides was established to be at least 6-fold more stable than unmodified oligonucleotides. Part II: Thiol terminated amine and guanidinium derivatives were synthesized and conjugated to 5 nm and 10 nm gold nanoparticles. These functionalized gold colloids were studied for their cellular uptake.