Table 1.

Selected preclinical studies for DNA-encoded biologics

Target	Disease etiology	Biologic class	Major findings	Ref.
Zika virus	Infectious	DMAb	Dual or single plasmid DNA delivery system results in expression of ZIKV neutralizing antibodies and serum from DMAb immunized mice, protects naïve mice from ZIKV lethal challenge.	[38••]
Ebola virus	Infectious	DMAb	EBOV DMAbs confer 100% protection from lethal challenge in mice/.	[35,39]
P. Aeruginosa	Infectious	DMAb	Anti-Pseudomonas DMAB protects mice from lethal pneumonia challenge and synergizes with antibiotic therapy resulting in protection from Antibiotic-resistant pneumonia.	[40••]
B. burgdorferi	Infectious	DMAb	Anti-Borrelia DMAb protects mice from tick challenge and represents a novel method for blocking Lyme disease transmission.	[41]
HIV-1	Infectious	F(ab)	Anti-HIV envelope neutralizing VRC01 F(ab) is produced rapidly in vivo following DNA immunization and EP.	[31]
HIV-1	Infectious	Broadly neutralizing Abs	Multiple bNAbs expressed in mice and NHPs at high concentration simultaneously, for extended periods	[33••]
Dengue	Infectious	DMAb	Delivery of multiple neutralizing DMAbs protects against all DENV serotypes and prevents antibody-dependent enhancement.	[36]
Chikungunya virus	Infectious	DMAb	A single injection of DMAb prophylaxis protects mice from CHIKV challenge. Combination of DNA and DMAb immunization affords both rapid and long-term protection.	[37••]
Influenza	Infectious	DMAb	DMAbs targeting influenza A and B protect mice from lethal challenge.	[34,35]
HIV-1	Infectious	Ig-like molecule	Proof-of-concept study for DNA-based delivery of anti-HIV immunoadhesins and in vivo modulation of protein function.	[32••]
PD-1	Malignancy	DMAb	Anti-PD-1 DMAbs are produced rapidly and persist in mouse sera, extending therapeutic window of immune checkpoint blockade therapy.	[28••]
CTLA-4	Malignancy	DMAb	Anti-CTLA-4 DMAbs are rapidly produced in vivo and shrink tumors in mouse cancer models.	[29••]
HER2	Malignancy	DMAb/DBiTE	Anti-HER2 DMAb and a bispecific targeting HER2 and CD3 induce control of ovarian tumors in mice and prolong survival.	[30••]