They have been preparing for gene modifications for a long time

Wondering why worry about Zika, Ebola, H1N1 - Let me reintroduce you to our forgotten friend, DARPA.

One of DARPA’s program called ADEPT: PROTECT (Autonomous Diagnostics to Enable Prevention and Therapeutics: Prophylactic Options to Environmental and Contagious Threats) is aimed at “developing new platform technologies that could be safely and rapidly deployed to the U.S. population and military personnel to provide immediate protection in the event of an infectious outbreak or biological weapons attack”. One of the methods of delivery is called Electroporation in RNA Vaccines (1). *See COMMENTS for all the references.

DARPA’s ADEPT purpose is to overcome limitations of active immunization. DARPA seeks new methods of scalable passive immunization (***DID YOU ALL READ THAT – PASSIVE IMMUNIZATION, YES) intended to confer protection to a healthy adult for a period of time, suitable to a military mission requirement or in a public health setting, as an approach to firebreak a high-risk group against a highly transmissible disease (2).

In the Broad Agency Announcement Autonomous Diagnostics to Enable Prevention and Therapeutics: Prophylactic Options to Environmental and Contagious Threats (ADEPT-PROTECT), (2), DARPA requests that “Constructs should have the ability to be ‘turned off’ to levels below detection, or be permanently removed from the host/host cell, either by the inherent nature of the material or by design.

How do they plan to do this?

ADEPT - CCM-V aims to develop new RNA-based platforms (DNA) for vaccine design and manufacture. RNA-based platforms are produced much more rapidly than current protein-based vaccines, and these platforms use the body to produce the proteins typically included in conventional vaccines.

This platform can decrease vaccine production time from years to weeks. The potential advantages of RNA-based vaccines include not only the ability to encode the antigen—the component of the infectious disease or toxin necessary to initiate a series of cellular steps resulting in lasting immunity—but also to enhance the robustness of the immune response. Synthetic biology techniques and encoded elements could control the individual’s immune response to the antigen, thereby ensuring that each individual develops an effective response to the vaccine.

(1) http://www.darpa.mil/…/autonomous-diagnostics-to-enable…

(2) (2) Broad Agency Announcement Autonomous Diagnostics to Enable Prevention and Therapeutics: Prophylactic Options to Environmental and Contagious Threats (ADEPT-PROTECT) DARPA-BAA-13-03 NOVEMBER 1, 2012, p. 7). https://www.fbo.gov/index?s=opportunity&mode=form…

(3) DNA and RNA-based vaccines: principles, progress and prospects

Wolfgang W. Leitner, Han Ying, and Nicholas P. Restifo*

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986720/

(4) One of DARPA’s proposed method of delivery for RNA Vaccines–

Electroporation is a microbiology technique in which an electrical field is applied to cells in order to increase the permeability of the cell membrane, allowing chemicals, drugs, or DNA to be introduced into the cell.

To promote effective immunization, attempts are being made to deliver vaccines through carriers as they control the spatial and temporal presentation of antigens to immune system thus leading to their sustained release and targeting:

DNA VACCINE DELIVERY STRATEGIES

Physical methods

Techniques such as tattooing, gene gun, electroporation, ultrasound, and laser provide energy (electrical, ultrasonic, laser beam) that brings about a transient change in permeability of cell membrane thereby promoting the entry of immunogenic DNA into the cells. The cell permeability is restored on the removal of applied energy after a short time period.

CH Saroja, PK Lakshmi, and Shyamala Bhaskaran1

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465129/

(5) Electroporation - DARPA

http://fusion.net/…/darpa-thinks-it-has-a-solution-to…/

(6) Research on these delivery techniques - Noninvasive delivery technologies: respiratory delivery of vaccines.

Abstract

“This paper reviews the developments in noninvasive methods of drug delivery, with a focus on the delivery of vaccines via the respiratory tract. Recent results indicate that the respiratory system, and the nasal mucosa in particular, provide a valuable target site for immunisation against respiratory and mucosal pathogens. Vaccine delivery via the nasal and pulmonary routes each present distinct sets of performance requirements. Current delivery systems in development for both routes are reviewed herein. The storage and respiratory delivery of drugs and vaccines in powder form has been shown to provide improved stability and extended retention time in the respiratory mucosa. These features, in addition to the noninvasive nature of respiratory delivery, can provide benefits to public health vaccination campaigns, facilitating mass vaccination without the high cost of maintaining cold-chain storage.”

-(“Cold chain” refers to the process used to maintain optimal conditions during the transport, storage, and handling of vaccines, starting at the manufacturer and ending with the administration of the vaccine to the client. The optimum temperature for refrigerated vaccines is between +2°C and +8°C.)

http://www.ncbi.nlm.nih.gov/pubmed/16370942

(6) Needle-free vaccine delivery. Giudice EL1, Campbell JD. · 1Center for Vaccine Development, University of Maryland School of Medicine, 685 W. Baltimore Street, Room 480, Baltimore, MD 21201, USA. egiudice@peds.umaryland.edu

850-GettyImages-1139071824

Abstract

The search for methods of vaccine delivery not requiring a needle and syringe has been accelerated by recent concerns regarding pandemic disease, bioterrorism, and disease eradication campaigns. Needle-free vaccine delivery could aid in these mass vaccinations by increasing ease and speed of delivery, and by offering improved safety and compliance, decreasing costs, and reducing pain associated with vaccinations. In this article, we summarize the rationale for delivery of needle-free vaccines and discuss several methods currently in use and under development, focusing on needle-free injection devices, transcutaneous immunization, and mucosal immunization. Jet injectors are needle-free devices that deliver liquid vaccine through a nozzle orifice and penetrate the skin with a high-speed narrow stream. They generate improved or equivalent immune responses compared with needle and syringe. Powder injection, a form of jet injection using vaccines in powder form, may obviate the need for the “cold chain.” Transcutaneous immunization involves applying vaccine antigen and adjuvant to the skin, using a patch or “microneedles,” and can induce both systemic and mucosal immunity. Mucosal immunization has thus far been focused on oral, nasal, and aerosol vaccines. Promising newer technologies in oral vaccination include using attenuated bacteria as vectors and transgenic plant “edible” vaccines. Improved knowledge regarding the immune system and its responses to vaccination continues to inform vaccine technologies for needle-free vaccine delivery.

Delivery strategies to enhance mucosal vaccination Sandra Chadwick, Christina Kriegel & Mansoor Amiji† Northeastern University, Department of Pharmaceutical Sciences, 360 Huntington Avenue, 110 Mugar Life Science Building, Boston, 02115, USA

Traditionally, vaccines are administered by injection (e.g., intramuscular vaccination) and will most probably elicit systemic immune responses but only insufficient mucosal responses. On the other side, oral or respiratory immunization usually favors the development of mucosal antibodies and cellmediated immune responses. Additionally, an effective uptake by M-cells for presentation to the mucosal inductive tissue promotes enhanced mucosal immunity. Thereby, nasal or oral routes as examples of mucosal immunization sites offer promising routes of delivery in the future due to non-invasive delivery (especially in childhood vaccination), low personnel costs, high patient compliance, and ease of single and repeated administration facilitating its use in mass vaccination.

In addition to protein antigens and attenuated organisms, plasmid-DNA-based vaccination strategies have been shown to induce long-lived systemic and humoral immune responses, but fail without a protective and targeted delivery system due to low cellular uptake and transfection and the likelihood of degradation and elimination before reaching their target organ and cells of interest.

https://www.researchgate.net/…/02bfe50e992c2e35bd000000…

(7) http://sitn.hms.harvard.edu/…/rna-vaccines-a-novel…/

(8) http://chemistry.about.com/…/lectu…/a/Dna-Versus-Rna.htm

(9) http://exploringorigins.org/rna.html

(10) http://www.who.int/biologicals/areas/vaccines/dna/en/

(11) http://www.darpa.mil/…/autonomous-diagnostics-to-enable…

(12) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465129/#ref39

(13) https://en.wikipedia.org/wiki/Vectors_in_gene_therapy…

(14) http://www.geoengineeringwatch.org/vaccinations-from-the…/

(15) https://www.researchgate.net/…/0deec51d37618b2a16000000…

(16) http://www.ncbi.nlm.nih.gov/pubmed/19931581

(17) http://www.ncbi.nlm.nih.gov/pubmed/21822816

(18) http://www.ncbi.nlm.nih.gov/pubmed/16564111

(19) http://search.hhs.gov/search?q=Vaccine+2016&HHS=Search&site=HHS&entqr=3&ud=1&sort=date:D:L:d1&output=xml_no_dtd&ie=UTF-8&oe=UTF-8&lr=lang_en&client=HHS&proxystylesheet=HHS&ulang=en&access=p&entqrm=0&entsp=a__ocr_policy&wc=200&wc_mc=1&&start=20

(20) http://www.fda.gov/…/VaccinesandRelatedBi…/ucm474746.htm

(21) http://www.darpa.mil/…/TestimonyArchived(March%2013…

(22) http://hub.hku.hk/handle/10722/161606

(23) http://www.ncbi.nlm.nih.gov/pubmed/18502000

(24) https://en.wikipedia.org/wiki/Sonoporation

(25) http://www.google.com/patents/WO2015085043A1?cl=en

(26) http://eboladeception.com/darpa-gives-45-million-grant…/

(27) http://www.ncbi.nlm.nih.gov/pubmed/16564111

(1) http://www.darpa.mil/…/autonomous-diagnostics-to-enable…

(2) Broad Agency Announcement Autonomous Diagnostics to Enable Prevention and Therapeutics: Prophylactic Options to Environmental and Contagious Threats (ADEPT-PROTECT) DARPA-BAA-13-03 NOVEMBER 1, 2012, p. 7). https://www.fbo.gov/index?s=opportunity&mode=form…

DNA and RNA-based vaccines: principles, progress and prospects

Wolfgang W. Leitner, Han Ying, and Nicholas P. Restifo*

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986720/

One of DARPA’s proposed method of delivery for RNA Vaccines–

Electroporation is a microbiology technique in which an electrical field is applied to cells in order to increase the permeability of the cell membrane, allowing chemicals, drugs, or DNA to be introduced into the cell.

To promote effective immunization, attempts are being made to deliver vaccines through carriers as they control the spatial and temporal presentation of antigens to immune system thus leading to their sustained release and targeting:

DNA VACCINE DELIVERY STRATEGIES

Physical methods

Techniques such as tattooing, gene gun, electroporation, ultrasound, and laser provide energy (electrical, ultrasonic, laser beam) that brings about a transient change in permeability of cell membrane thereby promoting the entry of immunogenic DNA into the cells. The cell permeability is restored on the removal of applied energy after a short time period.

CH Saroja, PK Lakshmi, and Shyamala Bhaskaran1

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465129/

Electroporation - DARPA

http://fusion.net/…/darpa-thinks-it-has-a-solution-to…/

Research on these delivery techniques -

Noninvasive delivery technologies: respiratory delivery of vaccines.

Abstract

“This paper reviews the developments in noninvasive methods of drug delivery, with a focus on the delivery of vaccines via the respiratory tract. Recent results indicate that the respiratory system, and the nasal mucosa in particular, provide a valuable target site for immunisation against respiratory and mucosal pathogens. Vaccine delivery via the nasal and pulmonary routes each present distinct sets of performance requirements. Current delivery systems in development for both routes are reviewed herein. The storage and respiratory delivery of drugs and vaccines in powder form has been shown to provide improved stability and extended retention time in the respiratory mucosa. These features, in addition to the noninvasive nature of respiratory delivery, can provide benefits to public health vaccination campaigns, facilitating mass vaccination without the high cost of maintaining cold-chain storage.”

-(“Cold chain” refers to the process used to maintain optimal conditions during the transport, storage, and handling of vaccines, starting at the manufacturer and ending with the administration of the vaccine to the client. The optimum temperature for refrigerated vaccines is between +2°C and +8°C.)

http://www.ncbi.nlm.nih.gov/pubmed/16370942

Needle-free vaccine delivery.

Giudice EL1, Campbell JD.

Author information

· 1Center for Vaccine Development, University of Maryland School of Medicine, 685 W. Baltimore Street, Room 480, Baltimore, MD 21201, USA. egiudice@peds.umaryland.edu

Abstract

The search for methods of vaccine delivery not requiring a needle and syringe has been accelerated by recent concerns regarding pandemic disease, bioterrorism, and disease eradication campaigns. Needle-free vaccine delivery could aid in these mass vaccinations by increasing ease and speed of delivery, and by offering improved safety and compliance, decreasing costs, and reducing pain associated with vaccinations. In this article, we summarize the rationale for delivery of needle-free vaccines and discuss several methods currently in use and under development, focusing on needle-free injection devices, transcutaneous immunization, and mucosal immunization. Jet injectors are needle-free devices that deliver liquid vaccine through a nozzle orifice and penetrate the skin with a high-speed narrow stream. They generate improved or equivalent immune responses compared with needle and syringe. Powder injection, a form of jet injection using vaccines in powder form, may obviate the need for the “cold chain.” Transcutaneous immunization involves applying vaccine antigen and adjuvant to the skin, using a patch or “microneedles,” and can induce both systemic and mucosal immunity. Mucosal immunization has thus far been focused on oral, nasal, and aerosol vaccines. Promising newer technologies in oral vaccination include using attenuated bacteria as vectors and transgenic plant “edible” vaccines. Improved knowledge regarding the immune system and its responses to vaccination continues to inform vaccine technologies for needle-free vaccine delivery.

Delivery strategies to enhance mucosal vaccination Sandra Chadwick, Christina Kriegel & Mansoor Amiji† Northeastern University, Department of Pharmaceutical Sciences, 360 Huntington Avenue, 110 Mugar Life Science Building, Boston, 02115, USA

Traditionally, vaccines are administered by injection (e.g., intramuscular vaccination) and will most probably elicit systemic immune responses but only insufficient mucosal responses. On the other side, oral or respiratory immunization usually favors the development of mucosal antibodies and cellmediated immune responses. Additionally, an effective uptake by M-cells for presentation to the mucosal inductive tissue promotes enhanced mucosal immunity. Thereby, nasal or oral routes as examples of mucosal immunization sites offer promising routes of delivery in the future due to non-invasive delivery (especially in childhood vaccination), low personnel costs, high patient compliance, and ease of single and repeated administration facilitating its use in mass vaccination.

In addition to protein antigens and attenuated organisms, plasmid-DNA-based vaccination strategies have been shown to induce long-lived systemic and humoral immune responses, but fail without a protective and targeted delivery system due to low cellular uptake and transfection and the likelihood of degradation and elimination before reaching their target organ and cells of interest.

https://www.researchgate.net/…/02bfe50e992c2e35bd000000…

http://sitn.hms.harvard.edu/…/rna-vaccines-a-novel…/

http://chemistry.about.com/…/lectu…/a/Dna-Versus-Rna.htm

http://exploringorigins.org/rna.html

http://www.who.int/biologicals/areas/vaccines/dna/en/

http://www.darpa.mil/…/autonomous-diagnostics-to-enable…

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465129/#ref39

https://en.wikipedia.org/wiki/Vectors_in_gene_therapy…

http://www.geoengineeringwatch.org/vaccinations-from-the…/

https://www.researchgate.net/…/0deec51d37618b2a16000000…

http://www.ncbi.nlm.nih.gov/pubmed/19931581

http://www.ncbi.nlm.nih.gov/pubmed/21822816

http://www.ncbi.nlm.nih.gov/pubmed/16564111

http://search.hhs.gov/search?q=Vaccine+2016&HHS=Search&site=HHS&entqr=3&ud=1&sort=date:D:L:d1&output=xml_no_dtd&ie=UTF-8&oe=UTF-8&lr=lang_en&client=HHS&proxystylesheet=HHS&ulang=en&access=p&entqrm=0&entsp=a__ocr_policy&wc=200&wc_mc=1&&start=20

http://www.fda.gov/…/VaccinesandRelatedBi…/ucm474746.htm

http://www.darpa.mil/…/TestimonyArchived(March%2013…

http://hub.hku.hk/handle/10722/161606

http://www.ncbi.nlm.nih.gov/pubmed/18502000

https://en.wikipedia.org/wiki/Sonoporation

http://www.google.com/patents/WO2015085043A1?cl=en

http://eboladeception.com/darpa-gives-45-million-grant…/

http://www.ncbi.nlm.nih.gov/pubmed/16564111