Preclinical Safety Validation of a Stabilized Viral Vector Direct Injection Approach to the Cervical Spinal Cord

被引：19

作者：

Federici, Thais ^{[1
]}

Riley, Jonathan ^{[2
]}

Park, John ^{[3
]}

Bain, Mark ^{[3
]}

Boulis, Nicholas M. ^{[1
]}

机构：

[1] Emory Univ, Sch Med, Atlanta, GA 30322 USA

[2] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44195 USA

[3] Cleveland Clin, Inst Neurosci, Cleveland, OH 44195 USA

来源：

CTS-CLINICAL AND TRANSLATIONAL SCIENCE | 2009年 / 2卷 / 02期

关键词：

targeted delivery; gene therapy; cervical spinal cord; adeno-associated viral vector; pig; BRAIN-STEM; DELIVERY; TRANSPLANTATION; PERFUSION; SURVIVAL; CELLS; MODEL; MICE;

D O I：

10.1111/j.1752-8062.2008.00084.x

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

The current lack of a validated intraspinal delivery approach precludes translation of promising cell or viral-based therapeutics for treatment of varied spinal cord afflictions. We have developed a stabilized cervical microinjection platform with the intent of precise delivery to intraspinal sites of interest. Nine 30-40 kg female swine underwent coordinate-based microinjection AAV2-GFP at three injected volumes (10, 25, and 50 mu L (n = 3/group)) and matched infusion rates (1.0, 2.5, and 5.0 mu L/min) over a period (t = 10 minutes). Preliminary validation is provided by behavioral and targeting data demonstrating safe delivery of a viral vector carrying a fluorescent reporter gene to the cervical spinal cord ventral horn.

引用

页码：165 / 167

页数：3

共 11 条

[1]

ADENOVIRUS-MEDIATED GENE-THERAPY FOR EXPERIMENTAL SPINAL-CORD TUMORS - TUMORICIDAL EFFICACY AND FUNCTIONAL OUTCOME [J].

COLAK, A ;

GOODMAN, JC ;

CHEN, SH ;

WOO, SLC ;

GROSSMAN, RG ;

SHINE, HD .

BRAIN RESEARCH, 1995, 691 (1-2) :76-82

[2]

Neural stem cell transplantation can ameliorate the phenotype of a mouse model of spinal muscular atrophy [J].

Corti, Stefania ;

Nizzardo, Monica ;

Nardini, Martina ;

Donadoni, Chiara ;

Salani, Sabrina ;

Ronchi, Dario ;

Saladino, Francesca ;

Bordoni, Andreina ;

Fortunato, Francesco ;

Del Bo, Roberto ;

Papadimitriou, Dimitra ;

Locatelli, Federica ;

Menozzi, Giorgia ;

Strazzer, Sandra ;

Bresolin, Nereo ;

Comi, Giacomo R. .

JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (10) :3316-3330

[3]

Recovery from paralysis in adult rats using embryonic stem cells [J].

Deshpande, Deepa M. ;

Kim, Yun-Sook ;

Martinez, Tara ;

Carmen, Jessica ;

Dike, Sonny ;

Shats, Irina ;

Rubin, Lee L. ;

Drummond, Jennifer ;

Krishnan, Chitra ;

Hoke, Ahmet ;

Maragakis, Nicholas ;

Shefner, Jeremy ;

Rothstein, Jeffrey D. ;

Kerr, Douglas A. .

ANNALS OF NEUROLOGY, 2006, 60 (01) :32-44

[4]

Delivery of AAV-IGF-1 to the CNS extends survival in ALS mice through modification of aberrant glial cell activity [J].

Dodge, James C. ;

Haidet, Amanda M. ;

Yang, Wendy ;

Passini, Marco A. ;

Hester, Mark ;

Clarke, Jennifer ;

Roskelley, Eric M. ;

Treleaven, Christopher M. ;

Rizo, Liza ;

Martin, Heather ;

Kim, Soo H. ;

Kaspar, Rita ;

Taksir, Tatyana V. ;

Griffiths, Denise A. ;

Cheng, Seng H. ;

Shihabuddin, Lamya S. ;

Kaspar, Brian K. .

MOLECULAR THERAPY, 2008, 16 (06) :1056-1064

[5]

Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model [J].

Kaspar, BK ;

Lladó, J ;

Sherkat, N ;

Rothstein, JD ;

Gage, FH .

SCIENCE, 2003, 301 (5634) :839-842

[6]

Direct convective delivery of macromolecules to the spinal cord [J].

Lonser, RR ;

Gogate, N ;

Morrison, PF ;

Wood, JD ;

Oldfield, EH .

JOURNAL OF NEUROSURGERY, 1998, 89 (04) :616-622

[7]

Successful and safe perfusion of the primate brainstem: in vivo magnetic resonance imaging of macromolecular distribution during infusion [J].

Lonser, RR ;

Walbridge, S ;

Garmestani, K ;

Butman, JA ;

Walters, HA ;

Vortmeyer, AO ;

Morrison, PF ;

Brechbiel, MW ;

Oldfield, EH .

JOURNAL OF NEUROSURGERY, 2002, 97 (04) :905-913

[8]

Real-time image-guided direct convective perfusion of intrinsic brainstem lesions [J].

Lonser, Russell R. ;

Warren, Katherine E. ;

Butman, John A. ;

Quezado, Zenaide ;

Robison, Aaron ;

Walbridge, Stuart ;

Schiffman, Raphael ;

Merrill, Marsha ;

Walker, Marion L. ;

Park, Deric M. ;

Croteau, David ;

Brady, Roscoe O. ;

Oldfield, Edward H. .

JOURNAL OF NEUROSURGERY, 2007, 107 (01) :190-197

[9]

Homologous transplantation of neural stem cells to the injured spinal cord of mice [J].

Pallini, R ;

Vitiani, LR ;

Bez, A ;

Casalbore, P ;

Facchiano, F ;

Gerevini, VD ;

Falchetti, ML ;

Fernandez, E ;

Maira, G ;

Peschle, C ;

Parati, E .

NEUROSURGERY, 2005, 57 (05) :1014-1024

[10]

RILEY J, 2009, NEUROSURGER IN PRESS

← 1 2 →