PMID- 23496378
OWN - NLM
STAT- MEDLINE
DCOM- 20140117
LR  - 20130417
IS  - 1520-4812 (Electronic)
IS  - 1043-1802 (Linking)
VI  - 24
IP  - 4
DP  - 2013 Apr 17
TI  - Endosomolytic bioreducible poly(amido amine disulfide) polymer conjugates for the 
      in vivo systemic delivery of siRNA therapeutics.
PG  - 640-7
LID - 10.1021/bc300600a [doi]
AB  - Efficient siRNA delivery is dependent not only on the ability of the delivery 
      vehicle to target a specific organ but also on its ability to enable siRNA entry 
      into the cytoplasm of the target cells. Polymers with endosomolytic properties 
      are increasingly being used as siRNA delivery vehicles due to their potential to 
      facilitate endosomal escape and intracellular delivery. Addition of disulfide 
      bonds in the backbone of these polymers was expected to provide degradability 
      through reduction by glutathione in cytosol. This paper describes the synthesis 
      of new endosomolytic bioreducible poly(amido amine disulfide) polymers whose 
      lytic potential can be masked at physiological pH, but can be restored at acidic 
      endosomal pH. These polymer conjugates gave good in vitro knockdown (KD) and did 
      not demonstrate cytotoxicity in a MTS assay. Efficient mRNA KD for apolipoprotein 
      B in mouse liver was observed with these polyconjugates following intravenous 
      dosing.
FAU - Parmar, Rubina Giare
AU  - Parmar RG
AD  - Department of Medicinal Chemistry, Merck & Co. Inc, West Point, PA, USA. 
      rubina_parmar@merck.com
FAU - Busuek, Marina
AU  - Busuek M
FAU - Walsh, Eileen S
AU  - Walsh ES
FAU - Leander, Karen R
AU  - Leander KR
FAU - Howell, Bonnie J
AU  - Howell BJ
FAU - Sepp-Lorenzino, Laura
AU  - Sepp-Lorenzino L
FAU - Kemp, Eric
AU  - Kemp E
FAU - Crocker, Louis S
AU  - Crocker LS
FAU - Leone, Anthony
AU  - Leone A
FAU - Kochansky, Christopher J
AU  - Kochansky CJ
FAU - Carr, Brian A
AU  - Carr BA
FAU - Garbaccio, Robert M
AU  - Garbaccio RM
FAU - Colletti, Steven L
AU  - Colletti SL
FAU - Wang, Weimin
AU  - Wang W
LA  - eng
PT  - Journal Article
DEP - 20130325
PL  - United States
TA  - Bioconjug Chem
JT  - Bioconjugate chemistry
JID - 9010319
RN  - 0 (Apolipoproteins B)
RN  - 0 (Disulfides)
RN  - 0 (Poly(amidoamine))
RN  - 0 (Polyamines)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Animals
MH  - Apolipoproteins B/deficiency/genetics
MH  - Disulfides/*chemistry
MH  - *Drug Delivery Systems
MH  - Endosomes/*metabolism
MH  - Erythrocytes/drug effects
MH  - Gene Silencing/drug effects
MH  - Hemolysis/drug effects
MH  - Hep G2 Cells
MH  - Humans
MH  - Liver/drug effects/metabolism
MH  - Mice
MH  - Molecular Structure
MH  - Oxidation-Reduction
MH  - Polyamines/*chemistry
MH  - RNA, Messenger/drug effects/genetics
MH  - RNA, Small Interfering/*administration & dosage/pharmacology
EDAT- 2013/03/19 06:00
MHDA- 2014/01/18 06:00
CRDT- 2013/03/19 06:00
PHST- 2013/03/19 06:00 [entrez]
PHST- 2013/03/19 06:00 [pubmed]
PHST- 2014/01/18 06:00 [medline]
AID - 10.1021/bc300600a [doi]
PST - ppublish
SO  - Bioconjug Chem. 2013 Apr 17;24(4):640-7. doi: 10.1021/bc300600a. Epub 2013 Mar 
      25.