PMID- 28644959
OWN - NLM
STAT- MEDLINE
DCOM- 20180420
LR  - 20181113
IS  - 1879-2472 (Electronic)
IS  - 0049-3848 (Print)
IS  - 0049-3848 (Linking)
VI  - 156
DP  - 2017 Aug
TI  - Generation and characterization of aptamers targeting factor XIa.
PG  - 134-141
LID - S0049-3848(17)30379-1 [pii]
LID - 10.1016/j.thromres.2017.06.015 [doi]
AB  - BACKGROUND: The plasma protease factor XIa (FXIa) has become a target of interest 
      for therapeutics designed to prevent or treat thrombotic disorders. METHODS: We 
      used a solution-based, directed evolution approach called systematic evolution of 
      ligands by exponential enrichment (SELEX) to isolate RNA aptamers that target the 
      FXIa catalytic domain. RESULTS: Two aptamers, designated 11.16 and 12.7, were 
      identified that bound to previously identified anion binding and serpin bindings 
      sites on the FXIa catalytic domain. The aptamers were non-competitive inhibitors 
      of FXIa cleavage of a tripeptide chromogenic substrate and of FXIa activation of 
      factor IX. In normal human plasma, aptamer 12.7 significantly prolonged the aPTT 
      clotting time. CONCLUSIONS: The results show that novel inhibitors of FXIa can be 
      prepared using SELEX techniques. RNA aptamers can bind to distinct sites on the 
      FXIa catalytic domain and noncompetitively inhibit FXIa activity toward its 
      primary macromolecular substrate factor IX with different levels of potency. Such 
      compounds can be developed for use as therapeutic inhibitors.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Woodruff, R S
AU  - Woodruff RS
AD  - Department of Surgery, Duke University Medical Center, Durham, NC, United States; 
      University Program in Genetics and Genomics, Duke University, Durham, NC, United 
      States.
FAU - Ivanov, I
AU  - Ivanov I
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University 
      Medical Center, Nashville, TN, United States.
FAU - Verhamme, I M
AU  - Verhamme IM
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University 
      Medical Center, Nashville, TN, United States.
FAU - Sun, M-F
AU  - Sun MF
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University 
      Medical Center, Nashville, TN, United States.
FAU - Gailani, D
AU  - Gailani D
AD  - Department of Pathology, Microbiology and Immunology, Vanderbilt University 
      Medical Center, Nashville, TN, United States.
FAU - Sullenger, B A
AU  - Sullenger BA
AD  - Department of Surgery, Duke University Medical Center, Durham, NC, United States. 
      Electronic address: bruce.sullenger@duke.edu.
LA  - eng
GR  - U54 HL112307/HL/NHLBI NIH HHS/United States
GR  - R01 HL058837/HL/NHLBI NIH HHS/United States
GR  - R01 GM116184/GM/NIGMS NIH HHS/United States
GR  - R01 HL065222/HL/NHLBI NIH HHS/United States
GR  - R01 HL081326/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20170609
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Anticoagulants)
RN  - 0 (Aptamers, Nucleotide)
RN  - EC 3.4.21.27 (Factor XIa)
SB  - IM
CIN - Thromb Res. 2017 Aug;156:198. PMID: 28739204
MH  - Anticoagulants/*metabolism
MH  - Aptamers, Nucleotide/*metabolism
MH  - Factor XIa/*metabolism
MH  - Humans
PMC - PMC5697752
MID - NIHMS920337
OTO - NOTNLM
OT  - Anticoagulant agents
OT  - Blood coagulation
OT  - Factor IX
OT  - Factor XIa
OT  - RNA aptamers
COIS- Conflict of interest: Dr. Sullenger reports founding equity from Regado 
      Biosciences/Tobira, outside the submitted work; In addition, Dr. Sullenger has a 
      patent issued broadly relevant to the submitted work. Dr. Gailani reports grants 
      from National Institutes of Health HL58837, HL81326, GM116184, a member of the 
      advisory board of Aronora, grants and personal fees from Bayer, grants and 
      personal fees from Dyax, personal fees from Ionis, personal fees from Merck, 
      personal fees from Novartis, grants and personal fees from Ono, outside the 
      submitted work; In addition, Dr. Gailani has a patent U.S. Patent Application No. 
      13/140,115 with royalties paid.
EDAT- 2017/06/24 06:00
MHDA- 2018/04/21 06:00
PMCR- 2018/08/01
CRDT- 2017/06/24 06:00
PHST- 2017/02/01 00:00 [received]
PHST- 2017/05/04 00:00 [revised]
PHST- 2017/06/08 00:00 [accepted]
PHST- 2017/06/24 06:00 [pubmed]
PHST- 2018/04/21 06:00 [medline]
PHST- 2017/06/24 06:00 [entrez]
PHST- 2018/08/01 00:00 [pmc-release]
AID - S0049-3848(17)30379-1 [pii]
AID - 10.1016/j.thromres.2017.06.015 [doi]
PST - ppublish
SO  - Thromb Res. 2017 Aug;156:134-141. doi: 10.1016/j.thromres.2017.06.015. Epub 2017 
      Jun 9.