Aerosol Gene Therapy

Abstract

Gene therapy is a novel field of medicine that holds tremendous therapeutic potential for a variety of human diseases. Targeting of therapeutic gene delivery vectors to the lungs can be beneficial for treatment of various pulmonary diseases such as lung cancer, cystic fibrosis, pulmonary hypertension, alpha-1 antitrypsin deficiency, and asthma. Inhalation therapy using formulations delivered as aerosols targets the lungs through the pulmonary airways. The instant access and the high ratio of the drug deposited within the lungs noninvasively are the major advantages of aerosol delivery over other routes of administration. Delivery of gene formulations via aerosols is a relatively new field, which is less than a decade old. However, in this short period of time significant developments in aerosol delivery systems and vectors have resulted in major advances toward potential applications for various pulmonary diseases. This article will review these advances and the potential future applications of aerosol gene therapy technology.

Synthetic vectors for gene delivery: An overview of their evolution depending on routes of administration.

“…However, the difficulty in crossing the vascular endothelium remains a major obstacle for intravenous administration and increases the risk of embolism. Local administration is therefore preferred to the systemic route, because it circumvents endothelial barriers and increases the concentration of nanovectors in the pulmonary tract while reducing adverse systemic effects [127]. To obtain the greatest therapeutic effect, an appreciation of the extra-and intracellular barriers and how the chemical design of carriers could be adapted is required.…”

Poly(ester amine)-mediated, Aerosol-delivered Akt1 Small Interfering RNA Suppresses Lung Tumorigenesis

“…Two major advantages of aerosol delivery are instant access and high ratio of the drug/gene deposited within the lung noninvasively (43). In recent years, much effort has focused on the development of aerosol gene delivery technology for the treatment of diverse lung diseases, including cancer.…”

Terapia génica: opción terapéutica para neoplasias, infecciones y enfermedades monogénicas

“…[26][27][28] Actualmente se ensayan protocolos en donde los vectores con el gen terapéutico se vehiculizan mediante un aerosol, para que actúen directamente sobre el epitelio pulmonar. [29][30][31] En este punto es dable reflexionar que mientras algunas patologías exigen que la corrección genética se efectúe puntualmente en el tipo celular afectado (tal el planteo de la TG para la talasemia, en donde el ADN que codifica para una hemoglobina adecuada se debe introducir en cé-lulas eritroides), 14,32 en otras se puede introducir el gen terapéutico en diferentes tipos celulares, para corregir el defecto sistémico (tal el planteo de la TG a la hora de introducir un gen codificante de Factor IX para el tratamiento de la Hemofilia B). 33,34 En líneas generales, las enfermedades monogénicas ideales para aplicar TG serían aquellas en donde el gen involucrado estuviera clonado, secuenciado y con conocimiento sobre su expresión y regulación, que cupiese en un vector y que su sobreexpresión no resultara peligrosa.…”