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Re: Paulness post# 10081

Tuesday, 08/03/2004 10:46:32 PM

Tuesday, August 03, 2004 10:46:32 PM

Post# of 64738
Charles Densmore Jr., Ph.D.

Assistant Professor, Department of Molecular Physiology & Biophysics
Ph.D., University of Florida College of Medicine
Postdoctoral, Baylor College of Medicine

E-mail: charlesd@bcm.tmc.edu
Telephone: (713) 798-3603
Fax: (713) 798-3475




Research Interests

The development of polymer-based aerosol gene delivery technology for the treatment of cancer, cystic fibrosis, alpha-1-antitrypsin deficiency, diabetes and a wide range of other pulmonary genetic disorders.

Over the last several years, efforts have been focused on the development of aerosol nonviral gene delivery technology for the treatment of lung cancer and a variety of other pulmonary genetic disorders. This has involved finding appropriate nonviral DNA delivery vectors that both withstand the sheer forces of nebulization and also function optimally in the environment of the lungs and airways. This innovative and noninvasive approach to gene delivery must overcome a number of physiological and structural barriers which have, to date, limited success clinically. The screening of a wide range of cationic lipids and polymers has resulted in candidates that exhibit remarkably high transfection efficiencies in airway epithelial and other lung cells and have yielded very significant biological responses in both antitumor and genetic immunization studies. This noninvasive mode of delivering genes now appears to be associated with only a minimal immune response and low overall toxicity and results in gene expression detectable up to a month after a single aerosol exposure. Current efforts primarily involve the aerosol delivery of polyethylenimine-based formulations of a variety of tumor suppressor and cytokine genes for the treatment of several human and murine lung tumor models in mice. The delivery of polymer-based gene silencing formulations represents another ongoing government/industry-funded effort. We are also investigating the idea of combining gene, chemo- and radio-therapies to treat these and other cancers. In addition, the application of this technology to treat other pulmonary conditions such as asthma, alpha-1-antitrypsin deficiency and cystic fibrosis is being pursued through a number of collaborative efforts here at Baylor, at the M. D. Anderson Cancer Center and elsewhere in academia and in industry.







Selected Publications

Kinsey B, Densmore C, Orson F. (2004). Gene delivery to the lungs by polycations. Polymeric Gene Delivery: Principles and Applications. Edited by M. M. Amiji. (In Press)

Kinsey B, Densmore C, Orson F. (2004). Non-Viral Gene Delivery to the Lungs. Current Gene Therapy (accepted).

Densmore, CL. (2003). Polyethyleneimine-based Gene Therapy by Inhalation. Expert Opinion in Biological Therapy. 3(7):1083-1092.

Densmore, CL. (2003). The Re-Emergence of Aerosol Gene Delivery: A Viable Approach to Lung Cancer Therapy. Current Cancer Drug Targets. 3(4):275-86.

Jia SF, Worth LL, Densmore CL , Xu B, Duan X, Kleinerman ES. (2003). Aerosol gene therapy with PEI:IL-12 eradicates established osteosarcoma lung metastases. Clinical Cancer Research. 9(9):3462-8.

Koshkina NV, Agoulnik I, Melton S, Densmore CL, Knight V. (2003). Biodistribution and pharmacokinetics of aerosol and intravenously administered DNA-polyethyleneimine complexes: optimization of pulmonary delivery and retention. Molecular Therapy. 8(2):249-54.

Densmore CL, Gautam A, Waldrep JC, Knight V. (2002). Re-establishing gene therapy by aerosol using transfection-efficient, low toxicity DNA-polymer constructs. Respiratory Drug Delivery. 8:1-7.

Densmore CL, Kleinerman ES, Gautam A, Jia SF, Xu B, Worth LL, Waldrep JC, Fung YK, T'Ang A, Knight V. (2001). Growth suppression of established human osteosarcoma lung metastases in mice by aerosol gene therapy with PEI-p53 complexes. Cancer Gene Therapy. 8(9):619-27.

Densmore CL, Orson F, Xu B, Kinsey BM, Waldrep JC, Hua P, Bhogal B, Knight V. (2000). Aerosol delivery of robust PEI-DNA complexes for gene therapy and genetic immunization. Molecular Therapy. 1(2):180-8.



Contact Information

Charles Densmore Jr., Ph.D.
Department of Molecular Physiology and Biophysics
Baylor College of Medicine
One Baylor Plaza, BCM 335
Houston, Texas 77030

Telephone: (713) 798-3603
Fax: (713) 798-3475
E-mail: charlesd@bcm.tmc.edu



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