The proposed R03 pilot study will combine two traditional gene delivery vectors into a novel hybrid device with potential to surpass the gene delivery efficacy of either original vector. Biomaterials have been a primary vehicle to facilitate gene delivery due to their inherent biocompatibility and adjustable properties available to influence cellular delivery mechanisms. More recently, bacterial vectors have also been used for gene delivery and provide an orthogonal set of biological engineering parameters to further influence the cellular gene delivery process. In this work, a hybrid biomaterial-bacterial device will be generated that combines the best features of both individual vectors. More specifically, previous studies using either biomaterial or bacterial vectors for targeted antigen presenting cell gene delivery will now be combined in an effort to boost gene delivery efficacy to these particular cells. Improved gene delivery as a result of the new hybrid biomaterial- biological vectors will establish the technology as innovative. More importantly, the hybrid devices will provide a completely new platform for engineering design that includes disparate tools such as polymer chemistry and molecular biology to further modify and technically advance the potency of the vectors. This will be a key theme of future grant submissions as will be the application of the new devices, facilitated through established connections between Tufts'Schools of Engineering and Medicine, as genetic vaccines against infectious disease and cancer.

Public Health Relevance

Success will provide two health-related outcomes: 1) a completely new gene delivery device with biological and biomaterial engineering tools available for future optimization and 2) a broad platform technology to be dedicated to new disease models and more advanced therapeutic applications.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
7R03AI088485-02
Application #
8109967
Study Section
Special Emphasis Panel (ZRG1-BST-K (90))
Program Officer
Gondre-Lewis, Timothy A
Project Start
2010-07-15
Project End
2014-06-30
Budget Start
2011-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2011
Total Cost
$72,206
Indirect Cost
Name
State University of New York at Buffalo
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Jones, Charles H; Zhang, Guojian; Nayerhoda, Roozbeh et al. (2017) Comprehensive vaccine design for commensal disease progression. Sci Adv 3:e1701797
Li, Yi; Beitelshees, Marie; Fang, Lei et al. (2016) In situ pneumococcal vaccine production and delivery through a hybrid biological-biomaterial vector. Sci Adv 2:e1600264
Li, Yi; Hill, Andrew; Beitelshees, Marie et al. (2016) Directed vaccination against pneumococcal disease. Proc Natl Acad Sci U S A 113:6898-903
Beitelshees, Marie; Li, Yi; Pfeifer, Blaine A (2016) Enhancing vaccine effectiveness with delivery technology. Curr Opin Biotechnol 42:24-29
Hill, Andrew B; Chen, Mingfu; Chen, Chih-Kuang et al. (2016) Overcoming Gene-Delivery Hurdles: Physiological Considerations for Nonviral Vectors. Trends Biotechnol 34:91-105
Jones, Charles H; Gollakota, Akhila; Chen, Mingfu et al. (2015) Influence of molecular weight upon mannosylated bio-synthetic hybrids for targeted antigen presenting cell gene delivery. Biomaterials 58:103-11
Chung, Tai-Chun; Jones, Charles H; Gollakota, Akhila et al. (2015) Improved Escherichia coli Bactofection and Cytotoxicity by Heterologous Expression of Bacteriophage ?X174 Lysis Gene E. Mol Pharm 12:1691-700
Jones, Charles H; Chen, Mingfu; Ravikrishnan, Anitha et al. (2015) Mannosylated poly(beta-amino esters) for targeted antigen presenting cell immune modulation. Biomaterials 37:333-44
Jones, Charles H; Chen, Chih-Kuang; Chen, Mingfu et al. (2015) PEGylated cationic polylactides for hybrid biosynthetic gene delivery. Mol Pharm 12:846-56
Jones, Charles H; Chen, Mingfu; Gollakota, Akhila et al. (2015) Structure-Function Assessment of Mannosylated Poly(?-amino esters) upon Targeted Antigen Presenting Cell Gene Delivery. Biomacromolecules 16:1534-41

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