166
G. Yang and Y. Huang
26. Dunkelberger JR, Song WC (2010) Complement and its role in innate and adaptive immune
responses. Cell Res 20(1):34–50
27. Hageman GS, Luthert PJ, Chong NHV, Johnson LV, Anderson DH, Mullins RF (2001) An
integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at
the RPE-Bruch’s membrane interface in aging and age-related macular degeneration. Progress
in Retinal and Eye Research 20(6):705–732
28. Nozaki M, Raisler BJ, Sakurai E, Sarma JV, Barnum SR, Lambris JD, Chen Y, Zhang K,
Ambati BK, Baffi JZ, Ambati J (2006) Drusen complement components C3a and C5a promote
choroidal neovascularization. Proc Natl Acad Sci U S A 103(7):2328–2333
29. Brockmann C, Brockmann T, Dege S, Busch C, Kociok N, Vater A, Klussmann S,
Strauss O, Joussen AM (2015) Intravitreal inhibition of complement C5a reduces choroidal
neovascularization in mice. Graefes Arch Clin Exp Ophthalmol 253(10):1695–1704
30. Chi ZL, Yoshida T, Lambris JD, Iwata T (2010) Suppression of drusen formation by
compstatin, a peptide inhibitor of complement C3 activation, on cynomolgus monkey with
early-onset macular degeneration. Adv Exp Med Biol 703(0065–2598 Print):127–135
31. Reynolds R, Hartnett ME, Atkinson JP, Giclas PC, Rosner B, Seddon JM (2009) Plasma
complement components and activation fragments: associations with age-related macular
degeneration genotypes and phenotypes. Invest Ophthalmol Vis Sci 50(12):5818–5827
32. Kassa E, Ciulla TA, Hussain RM, Dugel PU (2019) Complement inhibition as a therapeutic
strategy in retinal disorders. Expert Opinion Biol Therapy 19(4):335–342
33. Versteeg HH, Heemskerk JW, Levi M, Reitsma PH (2013) New fundamentals in hemostasis.
Physiol Rev 93(1):327–358
34. Griffin JH, Zlokovic BV, Mosnier LO (2018) Activated protein C, protease activated receptor
1, and neuroprotection. Blood 132(2):159–169
35. Brake MA, Ivanciu L, Maroney SA, Martinez ND, Mast AE, Westrick RJ (2019) Assessing
blood clotting and coagulation factors in mice. Curr Protoc Mouse Biol 9(2):e61
36. Dahlback B (2017) Novel insights into the regulation of coagulation by factor V isoforms,
tissue factor pathway inhibitoralpha, and protein S. J Thromb Haemost 15(7):1241–1250
37. Higuchi Y, Kubota T, Koyanagi M, Maeda T, Feldman AM, Makino N (2012) Upregulation of anticoagulant proteins, protein S and tissue factor pathway inhibitor, in the mouse
myocardium with cardio-specific TNF-alpha overexpression. Am J Physiol Heart Circ Physiol
302(11):H2352–H2362
38. Bock LC, Griffin LC, Latham JA, Vermaas EH, Toole JJ (1992) Selection of single-strandedDNA molecules that bind and inhibit human thrombin. Nature 355(6360):564–566
39. Trinh TL, Zhu G, Xiao X, Puszyk W, Sefah K, Wu Q, Tan W, Liu C (2015) A synthetic
aptamer-drug adduct for targeted liver cancer therapy. PLoS ONE 10(11):e0136673
40. Rusconi CP, Scardino E, Layzer J, Pitoc GA, Ortel TL, Monroe D, Sullenger BA (2002) RNA
aptamers as reversible antagonists of coagulation factor IXa. Nature 419(6902):90–94
41. Smiley DA, Becker RC (2014) Factor IXa as a target for anticoagulation in thrombotic
disorders and conditions. Drug Discovery Today 19(9):1445–1453
42. Sullenger B, Woodruff R, Monroe DM (2012) Potent anticoagulant aptamer directed against
factor IXa blocks macromolecular substrate interaction. J Biol Chem 287(16):12779–12786
43. Povsic TJ, Wargin WA, Alexander JH, Krasnow J, Krolick M, Cohen MG, Mehran R,
Buller CE, Bode C, Zelenkofske SL, Rusconi CP, Becker RC, Investigators R (2011) Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients: RADAR
pharmacokinetic and pharmacodynamic substudy. Eur Heart J 32(19):2412–2419
44. Dyke CK, Steinhubl SR, Kleiman NS, Cannon RO, Aberle LG, Lin M, Myles SK, Melloni C,
Harrington RA, Alexander JH, Becker RC, Rusconi CP (2006) First-in-human experience of
an antidote-controlled anticoagulant using RNA aptamer technology−A phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity.
Circulation 114(23):2490–2497
45. Povsic TJ, Vavalle JP, Alexander JH, Aberle LH, Zelenkofske SL, Becker RC, Buller CE,
Cohen MG, Cornel JH, Kasprzak JD, Montalescot G, Fail PS, Sarembock IJ, Mehran R,
Investigators R (2014) Use of the REG1 anticoagulation system in patients with acute coronary
G. Yang and Y. Huang
26. Dunkelberger JR, Song WC (2010) Complement and its role in innate and adaptive immune
responses. Cell Res 20(1):34–50
27. Hageman GS, Luthert PJ, Chong NHV, Johnson LV, Anderson DH, Mullins RF (2001) An
integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at
the RPE-Bruch’s membrane interface in aging and age-related macular degeneration. Progress
in Retinal and Eye Research 20(6):705–732
28. Nozaki M, Raisler BJ, Sakurai E, Sarma JV, Barnum SR, Lambris JD, Chen Y, Zhang K,
Ambati BK, Baffi JZ, Ambati J (2006) Drusen complement components C3a and C5a promote
choroidal neovascularization. Proc Natl Acad Sci U S A 103(7):2328–2333
29. Brockmann C, Brockmann T, Dege S, Busch C, Kociok N, Vater A, Klussmann S,
Strauss O, Joussen AM (2015) Intravitreal inhibition of complement C5a reduces choroidal
neovascularization in mice. Graefes Arch Clin Exp Ophthalmol 253(10):1695–1704
30. Chi ZL, Yoshida T, Lambris JD, Iwata T (2010) Suppression of drusen formation by
compstatin, a peptide inhibitor of complement C3 activation, on cynomolgus monkey with
early-onset macular degeneration. Adv Exp Med Biol 703(0065–2598 Print):127–135
31. Reynolds R, Hartnett ME, Atkinson JP, Giclas PC, Rosner B, Seddon JM (2009) Plasma
complement components and activation fragments: associations with age-related macular
degeneration genotypes and phenotypes. Invest Ophthalmol Vis Sci 50(12):5818–5827
32. Kassa E, Ciulla TA, Hussain RM, Dugel PU (2019) Complement inhibition as a therapeutic
strategy in retinal disorders. Expert Opinion Biol Therapy 19(4):335–342
33. Versteeg HH, Heemskerk JW, Levi M, Reitsma PH (2013) New fundamentals in hemostasis.
Physiol Rev 93(1):327–358
34. Griffin JH, Zlokovic BV, Mosnier LO (2018) Activated protein C, protease activated receptor
1, and neuroprotection. Blood 132(2):159–169
35. Brake MA, Ivanciu L, Maroney SA, Martinez ND, Mast AE, Westrick RJ (2019) Assessing
blood clotting and coagulation factors in mice. Curr Protoc Mouse Biol 9(2):e61
36. Dahlback B (2017) Novel insights into the regulation of coagulation by factor V isoforms,
tissue factor pathway inhibitoralpha, and protein S. J Thromb Haemost 15(7):1241–1250
37. Higuchi Y, Kubota T, Koyanagi M, Maeda T, Feldman AM, Makino N (2012) Upregulation of anticoagulant proteins, protein S and tissue factor pathway inhibitor, in the mouse
myocardium with cardio-specific TNF-alpha overexpression. Am J Physiol Heart Circ Physiol
302(11):H2352–H2362
38. Bock LC, Griffin LC, Latham JA, Vermaas EH, Toole JJ (1992) Selection of single-strandedDNA molecules that bind and inhibit human thrombin. Nature 355(6360):564–566
39. Trinh TL, Zhu G, Xiao X, Puszyk W, Sefah K, Wu Q, Tan W, Liu C (2015) A synthetic
aptamer-drug adduct for targeted liver cancer therapy. PLoS ONE 10(11):e0136673
40. Rusconi CP, Scardino E, Layzer J, Pitoc GA, Ortel TL, Monroe D, Sullenger BA (2002) RNA
aptamers as reversible antagonists of coagulation factor IXa. Nature 419(6902):90–94
41. Smiley DA, Becker RC (2014) Factor IXa as a target for anticoagulation in thrombotic
disorders and conditions. Drug Discovery Today 19(9):1445–1453
42. Sullenger B, Woodruff R, Monroe DM (2012) Potent anticoagulant aptamer directed against
factor IXa blocks macromolecular substrate interaction. J Biol Chem 287(16):12779–12786
43. Povsic TJ, Wargin WA, Alexander JH, Krasnow J, Krolick M, Cohen MG, Mehran R,
Buller CE, Bode C, Zelenkofske SL, Rusconi CP, Becker RC, Investigators R (2011) Pegnivacogin results in near complete FIX inhibition in acute coronary syndrome patients: RADAR
pharmacokinetic and pharmacodynamic substudy. Eur Heart J 32(19):2412–2419
44. Dyke CK, Steinhubl SR, Kleiman NS, Cannon RO, Aberle LG, Lin M, Myles SK, Melloni C,
Harrington RA, Alexander JH, Becker RC, Rusconi CP (2006) First-in-human experience of
an antidote-controlled anticoagulant using RNA aptamer technology−A phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity.
Circulation 114(23):2490–2497
45. Povsic TJ, Vavalle JP, Alexander JH, Aberle LH, Zelenkofske SL, Becker RC, Buller CE,
Cohen MG, Cornel JH, Kasprzak JD, Montalescot G, Fail PS, Sarembock IJ, Mehran R,
Investigators R (2014) Use of the REG1 anticoagulation system in patients with acute coronary